6-138908735-C-T
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The ENST00000450536.7(REPS1):c.2149G>A(p.Val717Ile) variant causes a missense change. The variant allele was found at a frequency of 0.151 in 1,613,634 control chromosomes in the GnomAD database, including 19,850 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.15 ( 1763 hom., cov: 32)
Exomes 𝑓: 0.15 ( 18087 hom. )
Consequence
REPS1
ENST00000450536.7 missense
ENST00000450536.7 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 4.33
Genes affected
REPS1 (HGNC:15578): (RALBP1 associated Eps domain containing 1) This gene encodes a signaling adaptor protein with two EH domains that interacts with proteins that participate in signaling, endocytosis and cytoskeletal changes. The encoded protein has been found in association with intersectin 1 and Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1 when intersectin 1 was isolated from clathrin-coated pits. The encoded protein has also been shown to interact with amphiphysin, a cytoplasmic protein at the surface of synaptic vesicles. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0013096929).
BP6
Variant 6-138908735-C-T is Benign according to our data. Variant chr6-138908735-C-T is described in ClinVar as [Benign]. Clinvar id is 1164210.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
REPS1 | NM_001286611.2 | c.2149G>A | p.Val717Ile | missense_variant | 18/20 | ENST00000450536.7 | NP_001273540.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
REPS1 | ENST00000450536.7 | c.2149G>A | p.Val717Ile | missense_variant | 18/20 | 1 | NM_001286611.2 | ENSP00000392065 | P4 |
Frequencies
GnomAD3 genomes AF: 0.148 AC: 22545AN: 152048Hom.: 1766 Cov.: 32
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GnomAD3 exomes AF: 0.123 AC: 30834AN: 251446Hom.: 2397 AF XY: 0.120 AC XY: 16376AN XY: 135900
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GnomAD4 exome AF: 0.151 AC: 221361AN: 1461468Hom.: 18087 Cov.: 32 AF XY: 0.148 AC XY: 107554AN XY: 727046
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GnomAD4 genome AF: 0.148 AC: 22539AN: 152166Hom.: 1763 Cov.: 32 AF XY: 0.145 AC XY: 10785AN XY: 74378
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;T;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T;T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.;.;.;.
MutationTaster
Benign
P;P;P;P;P
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
B;.;.;P;B;B
Vest4
MPC
0.20
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at