rs1931575

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000350.3(ABCA4):​c.1555-4141A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,140 control chromosomes in the GnomAD database, including 5,107 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5107 hom., cov: 32)

Consequence

ABCA4
NM_000350.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.199
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ABCA4NM_000350.3 linkuse as main transcriptc.1555-4141A>G intron_variant ENST00000370225.4 NP_000341.2
ABCA4XM_047416704.1 linkuse as main transcriptc.1555-4141A>G intron_variant XP_047272660.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABCA4ENST00000370225.4 linkuse as main transcriptc.1555-4141A>G intron_variant 1 NM_000350.3 ENSP00000359245 P1
ABCA4ENST00000649773.1 linkuse as main transcriptc.1555-4141A>G intron_variant ENSP00000496882

Frequencies

GnomAD3 genomes
AF:
0.250
AC:
38018
AN:
152022
Hom.:
5106
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.221
Gnomad AMI
AF:
0.192
Gnomad AMR
AF:
0.246
Gnomad ASJ
AF:
0.256
Gnomad EAS
AF:
0.600
Gnomad SAS
AF:
0.371
Gnomad FIN
AF:
0.224
Gnomad MID
AF:
0.213
Gnomad NFE
AF:
0.238
Gnomad OTH
AF:
0.250
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.250
AC:
38029
AN:
152140
Hom.:
5107
Cov.:
32
AF XY:
0.253
AC XY:
18817
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.221
Gnomad4 AMR
AF:
0.245
Gnomad4 ASJ
AF:
0.256
Gnomad4 EAS
AF:
0.600
Gnomad4 SAS
AF:
0.370
Gnomad4 FIN
AF:
0.224
Gnomad4 NFE
AF:
0.238
Gnomad4 OTH
AF:
0.256
Alfa
AF:
0.235
Hom.:
5708
Bravo
AF:
0.247
Asia WGS
AF:
0.483
AC:
1678
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
CADD
Benign
3.7
DANN
Benign
0.71

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.

Other links and lift over

dbSNP: rs1931575; hg19: chr1-94533014; API