chr1-94078579-A-AC

Position:

• chr1-94078579-A-AC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -1.16

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA4	NM_000350.3	c.1356+10dupG		intron_variant		ENST00000370225.4	NP_000341.2
ABCA4	XM_047416704.1	c.1356+10dupG		intron_variant
LOC124904222	XR_007066231.1	n.203-5144dupC		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA4	ENST00000370225.4	c.1356+10dupG		intron_variant		1	NM_000350.3	ENSP00000359245.3
ABCA4	ENST00000649773.1	c.1356+10dupG		intron_variant				ENSP00000496882.1

Frequencies

GnomAD3 genomes AF: 0.726 AC: 101824 AN: 140250 Hom.: 37396 Cov.: 0

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

GnomAD3 exomes AF: 0.743 AC: 183870 AN: 247414 Hom.: 69047 AF XY: 0.738 AC XY: 98741 AN XY: 133806

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 SAS exome AF: 0.651

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.: 22 AF XY: 0.680 AC XY: 345921 AN XY: 508446

Gnomad4 AFR exome AF: 0.540

Gnomad4 AMR exome AF: 0.772

Gnomad4 ASJ exome AF: 0.757

Gnomad4 EAS exome AF: 0.822

Gnomad4 SAS exome AF: 0.606

Gnomad4 FIN exome AF: 0.699

Gnomad4 NFE exome AF: 0.674

Gnomad4 OTH exome AF: 0.690

GnomAD4 genome AF: 0.726 AC: 101899 AN: 140360 Hom.: 37420 Cov.: 0 AF XY: 0.724 AC XY: 48772 AN XY: 67406

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.786

Gnomad4 ASJ AF: 0.785

Gnomad4 EAS AF: 0.827

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.698

Gnomad4 NFE AF: 0.768

Gnomad4 OTH AF: 0.726

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

Submissions by phenotype

not specified Benign:4

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 19, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Retinitis Pigmentosa, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Stargardt Disease, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Cone-Rod Dystrophy, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Macular degeneration Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs281865386; hg19: chr1-94544135;