Variant chr1-94083473-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000350.3(ABCA4):c.769-32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,535,706 control chromosomes in the GnomAD database, including 67,217 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4975 hom., cov: 32)

Exomes 𝑓: 0.29 ( 62242 hom. )

Consequence

ABCA4
NM_000350.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.649

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:

LOC124904222 (HGNC:):

LOC124904222 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 1-94083473-A-G is Benign according to our data. Variant chr1-94083473-A-G is described in ClinVar as [Benign]. Clinvar id is 99507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ABCA4	NM_000350.3 linkuse as main transcript	c.769-32T>C	intron_variant	ENST00000370225.4
LOC124904222	XR_007066231.1 linkuse as main transcript	n.203-256A>G	intron_variant, non_coding_transcript_variant
ABCA4	XM_047416704.1 linkuse as main transcript	c.769-32T>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA4	ENST00000370225.4 linkuse as main transcript	c.769-32T>C		intron_variant		1	NM_000350.3	P1
ABCA4	ENST00000649773.1 linkuse as main transcript	c.769-32T>C		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36500

AN:

151826

Hom.:

4969

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.213

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.315

Gnomad OTH

AF:

0.256

GnomAD3 exomes

AF:

0.245

AC:

60567

AN:

247468

Hom.:

7955

AF XY:

0.244

AC XY:

32808

AN XY:

134412

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.202

Gnomad ASJ exome

AF:

0.232

Gnomad EAS exome

AF:

0.195

Gnomad SAS exome

AF:

0.156

Gnomad FIN exome

AF:

0.250

Gnomad NFE exome

AF:

0.307

Gnomad OTH exome

AF:

0.262

GnomAD4 exome

AF:

0.293

AC:

405486

AN:

1383762

Hom.:

62242

Cov.:

AF XY:

0.289

AC XY:

199975

AN XY:

693042

show subpopulations

Gnomad4 AFR exome

AF:

0.114

Gnomad4 AMR exome

AF:

0.210

Gnomad4 ASJ exome

AF:

0.235

Gnomad4 EAS exome

AF:

0.223

Gnomad4 SAS exome

AF:

0.158

Gnomad4 FIN exome

AF:

0.252

Gnomad4 NFE exome

AF:

0.321

Gnomad4 OTH exome

AF:

0.266

GnomAD4 genome

AF:

0.240

AC:

36524

AN:

151944

Hom.:

4975

Cov.:

AF XY:

0.237

AC XY:

17581

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.120

Gnomad4 AMR

AF:

0.257

Gnomad4 ASJ

AF:

0.248

Gnomad4 EAS

AF:

0.214

Gnomad4 SAS

AF:

0.162

Gnomad4 FIN

AF:

0.254

Gnomad4 NFE

AF:

0.316

Gnomad4 OTH

AF:

0.254

Alfa

AF:

0.181

Hom.:

588

Bravo

AF:

0.235

Asia WGS

AF:

0.188

AC:

654

AN:

3476

ClinVar

Significance: 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

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

-0.74

CADD

Benign

1.6

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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