rs548122

Positions:

• chr1-94099874-C-G
• chr1-94099874-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000350.3(ABCA4):​c.571-883G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 151,998 control chromosomes in the GnomAD database, including 12,461 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12461 hom., cov: 32)
• Consequence: ABCA4 NM_000350.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA4	NM_000350.3	c.571-883G>C		intron_variant		ENST00000370225.4
ABCA4	XM_047416704.1	c.571-883G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA4	ENST00000370225.4	c.571-883G>C		intron_variant		1	NM_000350.3	P1
ABCA4	ENST00000649773.1	c.571-883G>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60449 AN: 151880 Hom.: 12446 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.406

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.398 AC: 60493 AN: 151998 Hom.: 12461 Cov.: 32 AF XY: 0.403 AC XY: 29930 AN XY: 74296

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.406

Alfa AF: 0.268 Hom.: 658

Bravo AF: 0.401

Asia WGS AF: 0.520 AC: 1808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.7
DANN	Benign	0.68

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: rs548122; hg19: chr1-94565430;