rs1801359

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000350.3(ABCA4):c.6249C>T(p.Ile2083Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0725 in 1,614,070 control chromosomes in the GnomAD database, including 6,526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. I2083I) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.13 ( 2077 hom., cov: 33)

Exomes 𝑓: 0.067 ( 4449 hom. )

Consequence

ABCA4
NM_000350.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12O:1

Conservation

PhyloP100: -1.43

Publications

19 publications found

Variant links:

Genes affected

ABCA4 (HGNC:34): (ATP binding cassette subfamily A member 4) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. This protein is a retina-specific ABC transporter with N-retinylidene-PE as a substrate. It is expressed exclusively in retina photoreceptor cells, and the gene product mediates transport of an essental molecule, all-trans-retinal aldehyde (atRAL), across the photoreceptor cell membrane. Mutations in this gene are found in patients diagnosed with Stargardt disease, a form of juvenile-onset macular degeneration. Mutations in this gene are also associated with retinitis pigmentosa-19, cone-rod dystrophy type 3, early-onset severe retinal dystrophy, fundus flavimaculatus, and macular degeneration age-related 2. [provided by RefSeq, Sep 2019]

ABCA4 Gene-Disease associations (from GenCC):

ABCA4-related retinopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
cone-rod dystrophy 3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
severe early-childhood-onset retinal dystrophy
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics
retinitis pigmentosa 19
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
cone-rod dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Stargardt disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ABCA4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 1-94001891-G-A is Benign according to our data. Variant chr1-94001891-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 99440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-94001891-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 99440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-94001891-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 99440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.43 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA4	NM_000350.3 link	c.6249C>T	p.Ile2083Ile	synonymous_variant	Exon 45 of 50	ENST00000370225.4	NP_000341.2	P78363Q6AI28
ABCA4	NM_001425324.1 link	c.6027C>T	p.Ile2009Ile	synonymous_variant	Exon 44 of 49		NP_001412253.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA4	ENST00000370225.4 link	c.6249C>T	p.Ile2083Ile	synonymous_variant	Exon 45 of 50	1	NM_000350.3	ENSP00000359245.3		P78363
ABCA4	ENST00000465352.1 link	n.665C>T		non_coding_transcript_exon_variant	Exon 6 of 6	5

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19385

AN:

152094

Hom.:

2080

Cov.:

show subpopulations

Gnomad AFR

AF:

0.293

Gnomad AMI

AF:

0.223

Gnomad AMR

AF:

0.0788

Gnomad ASJ

AF:

0.0974

Gnomad EAS

AF:

0.0583

Gnomad SAS

AF:

0.0704

Gnomad FIN

AF:

0.0334

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.0621

Gnomad OTH

AF:

0.119

GnomAD2 exomes

AF:

0.0767

AC:

19277

AN:

251396

AF XY:

0.0727

show subpopulations

Gnomad AFR exome

AF:

0.304

Gnomad AMR exome

AF:

0.0527

Gnomad ASJ exome

AF:

0.105

Gnomad EAS exome

AF:

0.0615

Gnomad FIN exome

AF:

0.0369

Gnomad NFE exome

AF:

0.0602

Gnomad OTH exome

AF:

0.0793

GnomAD4 exome

AF:

0.0668

AC:

97599

AN:

1461858

Hom.:

4449

Cov.:

AF XY:

0.0667

AC XY:

48512

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.307

AC:

10284

AN:

33478

American (AMR)

AF:

0.0552

AC:

2469

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.110

AC:

2875

AN:

26136

East Asian (EAS)

AF:

0.0507

AC:

2014

AN:

39700

South Asian (SAS)

AF:

0.0710

AC:

6124

AN:

86250

European-Finnish (FIN)

AF:

0.0368

AC:

1966

AN:

53418

Middle Eastern (MID)

AF:

0.125

AC:

722

AN:

5768

European-Non Finnish (NFE)

AF:

0.0594

AC:

66043

AN:

1111992

Other (OTH)

AF:

0.0845

AC:

5102

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

5676

11353

17029

22706

28382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2642

5284

7926

10568

13210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.127

AC:

19404

AN:

152212

Hom.:

2077

Cov.:

AF XY:

0.125

AC XY:

9287

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.293

AC:

12149

AN:

41490

American (AMR)

AF:

0.0785

AC:

1201

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0974

AC:

338

AN:

3470

East Asian (EAS)

AF:

0.0581

AC:

301

AN:

5184

South Asian (SAS)

AF:

0.0690

AC:

333

AN:

4824

European-Finnish (FIN)

AF:

0.0334

AC:

355

AN:

10620

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0621

AC:

4224

AN:

68004

Other (OTH)

AF:

0.123

AC:

259

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

776

1553

2329

3106

3882

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

198

396

594

792

990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0905

Hom.:

1560

Bravo

AF:

0.139

Asia WGS

AF:

0.111

AC:

388

AN:

3478

EpiCase

AF:

0.0692

EpiControl

AF:

0.0674

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jul 05, 2011

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Aug 25, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2Other:1

Retina International

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Retinitis Pigmentosa, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Stargardt Disease, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ABCA4-related disorder

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Cone-Rod Dystrophy, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinal dystrophy

Benign:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Severe early-childhood-onset retinal dystrophy;C1858806:Cone-rod dystrophy 3;C1866422:Retinitis pigmentosa 19;C3495438:Age related macular degeneration 2

Benign:1

Jul 15, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Macular degeneration

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

0.18

(source)

DANN

Benign

0.84

PhyloP100

-1.4

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over