Variant 1-93996081-C-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.6816+28G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0573 in 1,605,520 control chromosomes in the GnomAD database, including 7,645 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 3448 hom., cov: 32)

Exomes 𝑓: 0.048 ( 4197 hom. )

Consequence

ABCA4
NM_000350.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.268

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=-0.81).

BP6

Variant 1-93996081-C-G is Benign according to our data. Variant chr1-93996081-C-G is described in ClinVar as [Benign]. Clinvar id is 255927.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 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.6816+28G>C		intron_variant		ENST00000370225.4	NP_000341.2
ABCA4	XM_047416704.1 linkuse as main transcript	c.6594+28G>C		intron_variant			XP_047272660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA4	ENST00000370225.4 linkuse as main transcript	c.6816+28G>C		intron_variant		1	NM_000350.3	ENSP00000359245	P1

Frequencies

GnomAD3 genomes

AF:

0.142

AC:

21538

AN:

152042

Hom.:

3441

Cov.:

show subpopulations

Gnomad AFR

AF:

0.398

Gnomad AMI

AF:

0.0943

Gnomad AMR

AF:

0.0846

Gnomad ASJ

AF:

0.0617

Gnomad EAS

AF:

0.0226

Gnomad SAS

AF:

0.0542

Gnomad FIN

AF:

0.00509

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0408

Gnomad OTH

AF:

0.125

GnomAD3 exomes

AF:

0.0652

AC:

16307

AN:

250004

Hom.:

1639

AF XY:

0.0582

AC XY:

7860

AN XY:

135112

show subpopulations

Gnomad AFR exome

AF:

0.410

Gnomad AMR exome

AF:

0.0566

Gnomad ASJ exome

AF:

0.0681

Gnomad EAS exome

AF:

0.0270

Gnomad SAS exome

AF:

0.0498

Gnomad FIN exome

AF:

0.00590

Gnomad NFE exome

AF:

0.0397

Gnomad OTH exome

AF:

0.0634

GnomAD4 exome

AF:

0.0484

AC:

70375

AN:

1453360

Hom.:

4197

Cov.:

AF XY:

0.0476

AC XY:

34452

AN XY:

723506

show subpopulations

Gnomad4 AFR exome

AF:

0.410

Gnomad4 AMR exome

AF:

0.0601

Gnomad4 ASJ exome

AF:

0.0702

Gnomad4 EAS exome

AF:

0.0229

Gnomad4 SAS exome

AF:

0.0504

Gnomad4 FIN exome

AF:

0.00686

Gnomad4 NFE exome

AF:

0.0379

Gnomad4 OTH exome

AF:

0.0683

GnomAD4 genome

AF:

0.142

AC:

21579

AN:

152160

Hom.:

3448

Cov.:

AF XY:

0.137

AC XY:

10205

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.398

Gnomad4 AMR

AF:

0.0843

Gnomad4 ASJ

AF:

0.0617

Gnomad4 EAS

AF:

0.0224

Gnomad4 SAS

AF:

0.0530

Gnomad4 FIN

AF:

0.00509

Gnomad4 NFE

AF:

0.0408

Gnomad4 OTH

AF:

0.124

Alfa

AF:

0.0896

Hom.:

290

Bravo

AF:

0.160

Asia WGS

AF:

0.0630

AC:

220

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

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

-0.81

CADD

Benign

4.4

DANN

Benign

0.39

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