chr1-93993211-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000350.3(ABCA4):​c.*26C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,613,842 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0017 ( 13 hom. )

Consequence

ABCA4
NM_000350.3 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:5

Conservation

PhyloP100: 1.98
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 -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 1-93993211-G-T is Benign according to our data. Variant chr1-93993211-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 298221.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ABCA4NM_000350.3 linkuse as main transcriptc.*26C>A 3_prime_UTR_variant 50/50 ENST00000370225.4 NP_000341.2
ABCA4XM_047416704.1 linkuse as main transcriptc.*26C>A 3_prime_UTR_variant 49/49 XP_047272660.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABCA4ENST00000370225.4 linkuse as main transcriptc.*26C>A 3_prime_UTR_variant 50/501 NM_000350.3 ENSP00000359245 P1

Frequencies

GnomAD3 genomes
AF:
0.00181
AC:
276
AN:
152154
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000622
Gnomad FIN
AF:
0.0196
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000852
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.00226
AC:
568
AN:
250872
Hom.:
6
AF XY:
0.00213
AC XY:
289
AN XY:
135564
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000915
Gnomad FIN exome
AF:
0.0188
Gnomad NFE exome
AF:
0.00102
Gnomad OTH exome
AF:
0.00278
GnomAD4 exome
AF:
0.00167
AC:
2444
AN:
1461570
Hom.:
13
Cov.:
30
AF XY:
0.00165
AC XY:
1202
AN XY:
727096
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000812
Gnomad4 FIN exome
AF:
0.0207
Gnomad4 NFE exome
AF:
0.00107
Gnomad4 OTH exome
AF:
0.00124
GnomAD4 genome
AF:
0.00181
AC:
275
AN:
152272
Hom.:
3
Cov.:
32
AF XY:
0.00240
AC XY:
179
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.0196
Gnomad4 NFE
AF:
0.000853
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00100
Hom.:
0
Bravo
AF:
0.000348

ClinVar

Significance: Likely benign
Submissions summary: Benign:5
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Retinitis Pigmentosa, Recessive Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Stargardt Disease, Recessive Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
ABCA4-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Cone-Rod Dystrophy, Recessive Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Macular degeneration Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
CADD
Benign
14
DANN
Benign
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.18
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: rs200946608; hg19: chr1-94458767; API