chr1-93993444-A-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.6817-202T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 152,020 control chromosomes in the GnomAD database, including 1,036 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 1036 hom., cov: 32)

Consequence

ABCA4
NM_000350.3 intron

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 1.06
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 -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 1-93993444-A-T is Benign according to our data. Variant chr1-93993444-A-T is described in ClinVar as [Benign]. Clinvar id is 1259702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ABCA4NM_000350.3 linkuse as main transcriptc.6817-202T>A intron_variant ENST00000370225.4 NP_000341.2
ABCA4XM_047416704.1 linkuse as main transcriptc.6595-202T>A intron_variant XP_047272660.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABCA4ENST00000370225.4 linkuse as main transcriptc.6817-202T>A intron_variant 1 NM_000350.3 ENSP00000359245 P1

Frequencies

GnomAD3 genomes
AF:
0.0629
AC:
9552
AN:
151902
Hom.:
1031
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.219
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0224
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00145
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0443
Gnomad NFE
AF:
0.000941
Gnomad OTH
AF:
0.0425
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0630
AC:
9576
AN:
152020
Hom.:
1036
Cov.:
32
AF XY:
0.0611
AC XY:
4544
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.219
Gnomad4 AMR
AF:
0.0223
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00145
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000941
Gnomad4 OTH
AF:
0.0421
Alfa
AF:
0.0462
Hom.:
72
Bravo
AF:
0.0717
Asia WGS
AF:
0.0150
AC:
53
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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJul 14, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
7.7
DANN
Benign
0.75

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: rs17110718; hg19: chr1-94459000; API