Variant chr1-94014481-C-T 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.5460+62G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 1,589,402 control chromosomes in the GnomAD database, including 139,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12142 hom., cov: 31)

Exomes 𝑓: 0.42 ( 127421 hom. )

Consequence

ABCA4
NM_000350.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.786

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:

ABCA4 (HGNC:):

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=-0.93).

BP6

Variant 1-94014481-C-T is Benign according to our data. Variant chr1-94014481-C-T is described in ClinVar as [Benign]. Clinvar id is 1282828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.428 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.5460+62G>A		intron_variant		ENST00000370225.4	NP_000341.2	P78363Q6AI28
ABCA4	XM_047416704.1 linkuse as main transcript	c.5238+62G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA4	ENST00000370225.4 linkuse as main transcript	c.5460+62G>A		intron_variant		1	NM_000350.3	ENSP00000359245.3		P78363

Frequencies

GnomAD3 genomes

AF:

0.396

AC:

60100

AN:

151656

Hom.:

12140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.387

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.312

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.345

Gnomad FIN

AF:

0.474

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.433

Gnomad OTH

AF:

0.392

GnomAD4 exome

AF:

0.415

AC:

597162

AN:

1437628

Hom.:

127421

AF XY:

0.414

AC XY:

297054

AN XY:

716688

show subpopulations

Gnomad4 AFR exome

AF:

0.383

Gnomad4 AMR exome

AF:

0.248

Gnomad4 ASJ exome

AF:

0.411

Gnomad4 EAS exome

AF:

0.176

Gnomad4 SAS exome

AF:

0.357

Gnomad4 FIN exome

AF:

0.474

Gnomad4 NFE exome

AF:

0.435

Gnomad4 OTH exome

AF:

0.405

GnomAD4 genome

AF:

0.396

AC:

60137

AN:

151774

Hom.:

12142

Cov.:

AF XY:

0.394

AC XY:

29226

AN XY:

74172

show subpopulations

Gnomad4 AFR

AF:

0.387

Gnomad4 AMR

AF:

0.311

Gnomad4 ASJ

AF:

0.402

Gnomad4 EAS

AF:

0.143

Gnomad4 SAS

AF:

0.346

Gnomad4 FIN

AF:

0.474

Gnomad4 NFE

AF:

0.433

Gnomad4 OTH

AF:

0.395

Alfa

AF:

0.412

Hom.:

7750

Bravo

AF:

0.379

Asia WGS

AF:

0.273

AC:

952

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

2.3

DANN

Benign

0.67

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