1-94078579-AC-ACC

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000350.3(ABCA4):c.1356+10dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 1,125,016 control chromosomes in the GnomAD database, including 293,115 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 37420 hom., cov: 0)

Exomes 𝑓: 0.68 ( 255695 hom. )

Consequence

ABCA4
NM_000350.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.16

Publications

2 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:

LOC124904222 (HGNC:):

LOC124904222 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 1-94078579-A-AC is Benign according to our data. Variant chr1-94078579-A-AC is described in ClinVar as Benign. ClinVar VariationId is 193579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000350.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA4	NM_000350.3	MANE Select	c.1356+10dupG		intron	N/A	NP_000341.2
	ABCA4	NM_001425324.1		c.1356+10dupG		intron	N/A	NP_001412253.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA4	ENST00000370225.4	TSL:1 MANE Select	c.1356+10_1356+11insG		intron	N/A	ENSP00000359245.3
	ABCA4	ENST00000649773.1		c.1356+10_1356+11insG		intron	N/A	ENSP00000496882.1

Frequencies

GnomAD3 genomes

AF:

0.726

AC:

101824

AN:

140250

Hom.:

37396

Cov.:

show subpopulations

Gnomad AFR

AF:

0.621

Gnomad AMI

AF:

0.819

Gnomad AMR

AF:

0.786

Gnomad ASJ

AF:

0.785

Gnomad EAS

AF:

0.828

Gnomad SAS

AF:

0.675

Gnomad FIN

AF:

0.698

Gnomad MID

AF:

0.586

Gnomad NFE

AF:

0.768

Gnomad OTH

AF:

0.723

GnomAD2 exomes

AF:

0.743

AC:

183870

AN:

247414

AF XY:

0.738

show subpopulations

Gnomad AFR exome

AF:

0.621

Gnomad AMR exome

AF:

0.783

Gnomad ASJ exome

AF:

0.781

Gnomad EAS exome

AF:

0.815

Gnomad FIN exome

AF:

0.708

Gnomad NFE exome

AF:

0.764

Gnomad OTH exome

AF:

0.759

GnomAD4 exome

AF:

0.678

AC:

668025

AN:

984656

Hom.:

255695

Cov.:

AF XY:

0.680

AC XY:

345921

AN XY:

508446

show subpopulations

African (AFR)

AF:

0.540

AC:

13682

AN:

25328

American (AMR)

AF:

0.772

AC:

33097

AN:

42884

Ashkenazi Jewish (ASJ)

AF:

0.757

AC:

16874

AN:

22292

East Asian (EAS)

AF:

0.822

AC:

28915

AN:

35182

South Asian (SAS)

AF:

0.606

AC:

46739

AN:

77112

European-Finnish (FIN)

AF:

0.699

AC:

35146

AN:

50294

Middle Eastern (MID)

AF:

0.584

AC:

2780

AN:

4758

European-Non Finnish (NFE)

AF:

0.674

AC:

460683

AN:

683182

Other (OTH)

AF:

0.690

AC:

30109

AN:

43624

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

6903

13805

20708

27610

34513

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7964

15928

23892

31856

39820

<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:

0.726

AC:

101899

AN:

140360

Hom.:

37420

Cov.:

AF XY:

0.724

AC XY:

48772

AN XY:

67406

show subpopulations

African (AFR)

AF:

0.622

AC:

22991

AN:

36988

American (AMR)

AF:

0.786

AC:

10663

AN:

13566

Ashkenazi Jewish (ASJ)

AF:

0.785

AC:

2658

AN:

3388

East Asian (EAS)

AF:

0.827

AC:

3838

AN:

4642

South Asian (SAS)

AF:

0.676

AC:

2878

AN:

4260

European-Finnish (FIN)

AF:

0.698

AC:

5862

AN:

8404

Middle Eastern (MID)

AF:

0.585

AC:

166

AN:

284

European-Non Finnish (NFE)

AF:

0.768

AC:

50748

AN:

66056

Other (OTH)

AF:

0.726

AC:

1368

AN:

1884

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1222

2444

3665

4887

6109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<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:

0.726

Hom.:

5838

Asia WGS

AF:

0.787

AC:

2733

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

May 19, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Retinitis Pigmentosa, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Stargardt Disease, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Cone-Rod Dystrophy, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Macular degeneration

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over