GeneBe

rs765746708

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001288985.2(ABCA8):​c.4573G>T​(p.Val1525Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ABCA8
NM_001288985.2 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.745
Variant links:
Genes affected
ABCA8 (HGNC:38): (ATP binding cassette subfamily A member 8) 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. The encoded protein may regulate lipid metabolism and be involved in the formation and maintenance of myelin. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.077640295).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ABCA8NM_001288985.2 linkc.4573G>T p.Val1525Leu missense_variant Exon 37 of 40 ENST00000586539.6 NP_001275914.1 O94911-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ABCA8ENST00000586539.6 linkc.4573G>T p.Val1525Leu missense_variant Exon 37 of 40 1 NM_001288985.2 ENSP00000467271.1 O94911-3
ABCA8ENST00000430352.6 linkc.4558G>T p.Val1520Leu missense_variant Exon 36 of 39 1 ENSP00000402814.3 A0A0A0MSU4
ABCA8ENST00000269080.6 linkc.4453G>T p.Val1485Leu missense_variant Exon 35 of 38 1 ENSP00000269080.1 O94911-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461868
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
7.9
DANN
Benign
0.96
DEOGEN2
Benign
0.099
T;T;.
Eigen
Benign
-0.96
Eigen_PC
Benign
-0.98
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.43
T;T;T
M_CAP
Benign
0.036
D
MetaRNN
Benign
0.078
T;T;T
MetaSVM
Benign
-0.72
T
MutationAssessor
Benign
1.2
L;.;.
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-2.1
N;.;.
REVEL
Benign
0.10
Sift
Benign
0.046
D;.;.
Sift4G
Benign
0.17
T;T;T
Polyphen
0.031
B;.;.
Vest4
0.14
MutPred
0.32
Gain of helix (P = 0.062);.;.;
MVP
0.56
MPC
0.057
ClinPred
0.074
T
GERP RS
-0.98
Varity_R
0.12
gMVP
0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-66871459; API