rs145368920

chr1-94048993-G-Achr1-94048993-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000350.3(ABCA4):c.2654-36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,606,228 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (4 hom.)
• Consequence: ABCA4 NM_000350.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.283

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-94048993-G-A is Benign according to our data. Variant chr1-94048993-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 255918.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA4	NM_000350.3	c.2654-36C>T		intron_variant		ENST00000370225.4
ABCA4	XM_047416704.1	c.2432-36C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA4	ENST00000370225.4	c.2654-36C>T		intron_variant		1	NM_000350.3	P1
ABCA4	ENST00000649773.1	c.2432-36C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.00140 AC: 213 AN: 151944 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00356

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00206

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00126 AC: 316 AN: 250584 Hom.: 0 AF XY: 0.00141 AC XY: 191 AN XY: 135420

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.000753

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00144

Gnomad FIN exome AF: 0.000557

Gnomad NFE exome AF: 0.00193

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00169 AC: 2462 AN: 1454166 Hom.: 4 Cov.: 28 AF XY: 0.00172 AC XY: 1246 AN XY: 723924

Gnomad4 AFR exome AF: 0.000240

Gnomad4 AMR exome AF: 0.000917

Gnomad4 ASJ exome AF: 0.0000767

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00135

Gnomad4 FIN exome AF: 0.000375

Gnomad4 NFE exome AF: 0.00197

Gnomad4 OTH exome AF: 0.00161

GnomAD4 genome AF: 0.00139 AC: 212 AN: 152062 Hom.: 2 Cov.: 32 AF XY: 0.00124 AC XY: 92 AN XY: 74324

Gnomad4 AFR AF: 0.000603

Gnomad4 AMR AF: 0.00164

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00335

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00206

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00126 Hom.: 0

Bravo AF: 0.00139

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	5.7
Dann	Benign	0.58

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: rs145368920; hg19: chr1-94514549;