Variant rs56197337 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.2160+49T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0495 in 1,560,890 control chromosomes in the GnomAD database, including 2,075 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 258 hom., cov: 32)

Exomes 𝑓: 0.049 ( 1817 hom. )

Consequence

ABCA4
NM_000350.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.238

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:

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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=-0.88).

BP6

Variant 1-94060488-A-G is Benign according to our data. Variant chr1-94060488-A-G is described in ClinVar as [Benign]. Clinvar id is 255917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA4	NM_000350.3 linkuse as main transcript	c.2160+49T>C		intron_variant		ENST00000370225.4	NP_000341.2
ABCA4	XM_047416704.1 linkuse as main transcript	c.2160+49T>C		intron_variant			XP_047272660.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
ABCA4	ENST00000370225.4 linkuse as main transcript	c.2160+49T>C	intron_variant	1	NM_000350.3	ENSP00000359245	P1
ABCA4	ENST00000649773.1 linkuse as main transcript	c.2160+49T>C	intron_variant			ENSP00000496882
ABCA4	ENST00000472033.1 linkuse as main transcript	n.280+49T>C	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.0541

AC:

8230

AN:

152176

Hom.:

250

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0682

Gnomad AMI

AF:

0.0352

Gnomad AMR

AF:

0.0746

Gnomad ASJ

AF:

0.0207

Gnomad EAS

AF:

0.0375

Gnomad SAS

AF:

0.0595

Gnomad FIN

AF:

0.0395

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0461

Gnomad OTH

AF:

0.0554

GnomAD3 exomes

AF:

0.0499

AC:

12426

AN:

249258

Hom.:

333

AF XY:

0.0492

AC XY:

6637

AN XY:

134804

show subpopulations

Gnomad AFR exome

AF:

0.0691

Gnomad AMR exome

AF:

0.0719

Gnomad ASJ exome

AF:

0.0221

Gnomad EAS exome

AF:

0.0404

Gnomad SAS exome

AF:

0.0582

Gnomad FIN exome

AF:

0.0431

Gnomad NFE exome

AF:

0.0437

Gnomad OTH exome

AF:

0.0442

GnomAD4 exome

AF:

0.0490

AC:

69055

AN:

1408596

Hom.:

1817

Cov.:

AF XY:

0.0487

AC XY:

34257

AN XY:

704014

show subpopulations

Gnomad4 AFR exome

AF:

0.0720

Gnomad4 AMR exome

AF:

0.0711

Gnomad4 ASJ exome

AF:

0.0213

Gnomad4 EAS exome

AF:

0.0427

Gnomad4 SAS exome

AF:

0.0561

Gnomad4 FIN exome

AF:

0.0440

Gnomad4 NFE exome

AF:

0.0480

Gnomad4 OTH exome

AF:

0.0492

GnomAD4 genome

AF:

0.0543

AC:

8266

AN:

152294

Hom.:

258

Cov.:

AF XY:

0.0545

AC XY:

4056

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0687

Gnomad4 AMR

AF:

0.0751

Gnomad4 ASJ

AF:

0.0207

Gnomad4 EAS

AF:

0.0376

Gnomad4 SAS

AF:

0.0597

Gnomad4 FIN

AF:

0.0395

Gnomad4 NFE

AF:

0.0461

Gnomad4 OTH

AF:

0.0553

Alfa

AF:

0.0473

Hom.:

Bravo

AF:

0.0574

Asia WGS

AF:

0.0490

AC:

170

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.88

CADD

Benign

6.0

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

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