rs472908

Positions:

chr1-94021798-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000350.3(ABCA4):c.4773+48C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 1,606,414 control chromosomes in the GnomAD database, including 269,572 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 29725 hom., cov: 31)

Exomes 𝑓: 0.57 ( 239847 hom. )

Consequence

ABCA4
NM_000350.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: -0.444

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 links:

ABCA4 (HGNC:):

ABCA4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-94021798-G-A is Benign according to our data. Variant chr1-94021798-G-A is described in ClinVar as [Benign]. Clinvar id is 99319.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA4	NM_000350.3 linkuse as main transcript	c.4773+48C>T		intron_variant		ENST00000370225.4	NP_000341.2	P78363Q6AI28
ABCA4	XM_047416704.1 linkuse as main transcript	c.4551+48C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA4	ENST00000370225.4 linkuse as main transcript	c.4773+48C>T		intron_variant		1	NM_000350.3	ENSP00000359245.3		P78363
ABCA4	ENST00000460514.1 linkuse as main transcript	n.267+48C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.619

AC:

94022

AN:

151824

Hom.:

29678

Cov.:

show subpopulations

Gnomad AFR

AF:

0.742

Gnomad AMI

AF:

0.509

Gnomad AMR

AF:

0.607

Gnomad ASJ

AF:

0.624

Gnomad EAS

AF:

0.454

Gnomad SAS

AF:

0.543

Gnomad FIN

AF:

0.620

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.568

Gnomad OTH

AF:

0.583

GnomAD3 exomes

AF:

0.584

AC:

146325

AN:

250422

Hom.:

43571

AF XY:

0.578

AC XY:

78368

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.752

Gnomad AMR exome

AF:

0.670

Gnomad ASJ exome

AF:

0.622

Gnomad EAS exome

AF:

0.447

Gnomad SAS exome

AF:

0.552

Gnomad FIN exome

AF:

0.608

Gnomad NFE exome

AF:

0.559

Gnomad OTH exome

AF:

0.562

GnomAD4 exome

AF:

0.572

AC:

831607

AN:

1454472

Hom.:

239847

Cov.:

AF XY:

0.571

AC XY:

413306

AN XY:

724100

show subpopulations

Gnomad4 AFR exome

AF:

0.755

Gnomad4 AMR exome

AF:

0.661

Gnomad4 ASJ exome

AF:

0.623

Gnomad4 EAS exome

AF:

0.463

Gnomad4 SAS exome

AF:

0.552

Gnomad4 FIN exome

AF:

0.605

Gnomad4 NFE exome

AF:

0.565

Gnomad4 OTH exome

AF:

0.577

GnomAD4 genome

AF:

0.620

AC:

94129

AN:

151942

Hom.:

29725

Cov.:

AF XY:

0.621

AC XY:

46083

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.742

Gnomad4 AMR

AF:

0.607

Gnomad4 ASJ

AF:

0.624

Gnomad4 EAS

AF:

0.454

Gnomad4 SAS

AF:

0.543

Gnomad4 FIN

AF:

0.620

Gnomad4 NFE

AF:

0.568

Gnomad4 OTH

AF:

0.588

Alfa

AF:

0.573

Hom.:

45251

Bravo

AF:

0.627

Asia WGS

AF:

0.527

AC:

1833

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	literature only	Retina International	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 23953153, 27884173, 29555955) -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 13, 2022	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 01, 2016	- -

Age related macular degeneration 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Severe early-childhood-onset retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Retinitis pigmentosa 19

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Cone-rod dystrophy 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.80

DANN

Benign

0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over