rs12070273

Positions:

• chr1-94000532-A-G

Variant summary

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

The NM_000350.3(ABCA4):​c.6479+304T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,132 control chromosomes in the GnomAD database, including 2,038 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 0.13 (2038 hom., cov: 33)
• Consequence: ABCA4 NM_000350.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.554

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA4	NM_000350.3	c.6479+304T>C		intron_variant		ENST00000370225.4	NP_000341.2
ABCA4	XM_047416704.1	c.6257+304T>C		intron_variant			XP_047272660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA4	ENST00000370225.4	c.6479+304T>C		intron_variant		1	NM_000350.3	ENSP00000359245	P1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19321 AN: 152012 Hom.: 2040 Cov.: 33

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.0787

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.0571

Gnomad SAS AF: 0.0710

Gnomad FIN AF: 0.0332

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0622

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.127 AC: 19342 AN: 152132 Hom.: 2038 Cov.: 33 AF XY: 0.125 AC XY: 9266 AN XY: 74388

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.0784

Gnomad4 ASJ AF: 0.0974

Gnomad4 EAS AF: 0.0568

Gnomad4 SAS AF: 0.0696

Gnomad4 FIN AF: 0.0332

Gnomad4 NFE AF: 0.0622

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0740 Hom.: 1137

Bravo AF: 0.139

Asia WGS AF: 0.111 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.48

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: rs12070273; hg19: chr1-94466088;