Variant chr1-94062803-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000350.3(ABCA4):c.1761-50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 1,585,642 control chromosomes in the GnomAD database, including 255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 12 hom., cov: 32)

Exomes 𝑓: 0.017 ( 243 hom. )

Consequence

ABCA4
NM_000350.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: 0.0770

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:

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=-0.86).

BP6

Variant 1-94062803-C-T is Benign according to our data. Variant chr1-94062803-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 99078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0121 (1848/152240) while in subpopulation NFE AF= 0.0194 (1320/68014). AF 95% confidence interval is 0.0185. There are 12 homozygotes in gnomad4. There are 879 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA4	NM_000350.3 linkuse as main transcript	c.1761-50G>A		intron_variant		ENST00000370225.4
ABCA4	XM_047416704.1 linkuse as main transcript	c.1761-50G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA4	ENST00000370225.4 linkuse as main transcript	c.1761-50G>A		intron_variant		1	NM_000350.3	P1
ABCA4	ENST00000649773.1 linkuse as main transcript	c.1761-50G>A		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0121

AC:

1847

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00309

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00963

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00788

Gnomad FIN

AF:

0.0101

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0194

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.0141

AC:

3236

AN:

228846

Hom.:

AF XY:

0.0144

AC XY:

1771

AN XY:

123364

show subpopulations

Gnomad AFR exome

AF:

0.00253

Gnomad AMR exome

AF:

0.0103

Gnomad ASJ exome

AF:

0.0259

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00868

Gnomad FIN exome

AF:

0.00898

Gnomad NFE exome

AF:

0.0202

Gnomad OTH exome

AF:

0.0216

GnomAD4 exome

AF:

0.0168

AC:

24061

AN:

1433402

Hom.:

243

Cov.:

AF XY:

0.0168

AC XY:

11999

AN XY:

712904

show subpopulations

Gnomad4 AFR exome

AF:

0.00240

Gnomad4 AMR exome

AF:

0.0108

Gnomad4 ASJ exome

AF:

0.0244

Gnomad4 EAS exome

AF:

0.0000509

Gnomad4 SAS exome

AF:

0.00957

Gnomad4 FIN exome

AF:

0.0116

Gnomad4 NFE exome

AF:

0.0186

Gnomad4 OTH exome

AF:

0.0166

GnomAD4 genome

AF:

0.0121

AC:

1848

AN:

152240

Hom.:

Cov.:

AF XY:

0.0118

AC XY:

879

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00310

Gnomad4 AMR

AF:

0.00961

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00789

Gnomad4 FIN

AF:

0.0101

Gnomad4 NFE

AF:

0.0194

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0187

Hom.:

Bravo

AF:

0.0117

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
not provided, no classification provided	literature only	Retina International	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.1

DANN

Benign

0.80

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

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