chr1-94008340-G-T

Position:

chr1-94008340-G-T

Variant summary

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

The NM_000350.3(ABCA4):c.5836-43C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,583,010 control chromosomes in the GnomAD database, including 25,537 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 2935 hom., cov: 32)

Exomes 𝑓: 0.18 ( 22602 hom. )

Consequence

ABCA4
NM_000350.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.277

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 1-94008340-G-T is Benign according to our data. Variant chr1-94008340-G-T is described in ClinVar as [Benign]. Clinvar id is 255925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA4	NM_000350.3 linkuse as main transcript	c.5836-43C>A		intron_variant		ENST00000370225.4
ABCA4	XM_047416704.1 linkuse as main transcript	c.5614-43C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA4	ENST00000370225.4 linkuse as main transcript	c.5836-43C>A		intron_variant		1	NM_000350.3	P1
ABCA4	ENST00000465352.1 linkuse as main transcript	n.252-43C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

29315

AN:

152084

Hom.:

2924

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.212

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.172

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.179

GnomAD3 exomes

AF:

0.172

AC:

43169

AN:

250740

Hom.:

3882

AF XY:

0.170

AC XY:

23008

AN XY:

135524

show subpopulations

Gnomad AFR exome

AF:

0.235

Gnomad AMR exome

AF:

0.155

Gnomad ASJ exome

AF:

0.202

Gnomad EAS exome

AF:

0.127

Gnomad SAS exome

AF:

0.133

Gnomad FIN exome

AF:

0.174

Gnomad NFE exome

AF:

0.183

Gnomad OTH exome

AF:

0.175

GnomAD4 exome

AF:

0.175

AC:

250587

AN:

1430808

Hom.:

22602

Cov.:

AF XY:

0.174

AC XY:

124243

AN XY:

713670

show subpopulations

Gnomad4 AFR exome

AF:

0.242

Gnomad4 AMR exome

AF:

0.159

Gnomad4 ASJ exome

AF:

0.202

Gnomad4 EAS exome

AF:

0.135

Gnomad4 SAS exome

AF:

0.131

Gnomad4 FIN exome

AF:

0.176

Gnomad4 NFE exome

AF:

0.178

Gnomad4 OTH exome

AF:

0.173

GnomAD4 genome

AF:

0.193

AC:

29376

AN:

152202

Hom.:

2935

Cov.:

AF XY:

0.190

AC XY:

14139

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.236

Gnomad4 AMR

AF:

0.165

Gnomad4 ASJ

AF:

0.212

Gnomad4 EAS

AF:

0.131

Gnomad4 SAS

AF:

0.128

Gnomad4 FIN

AF:

0.172

Gnomad4 NFE

AF:

0.186

Gnomad4 OTH

AF:

0.183

Alfa

AF:

0.178

Hom.:

3168

Bravo

AF:

0.194

Asia WGS

AF:

0.146

AC:

508

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Age related macular degeneration 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Severe early-childhood-onset retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Retinitis pigmentosa 19

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Cone-rod dystrophy 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

4.9

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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