rs186928850
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_170604.3(RASGRP4):c.1490A>T(p.Asn497Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 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)
Consequence
RASGRP4
NM_170604.3 missense
NM_170604.3 missense
Scores
1
5
13
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.52
Genes affected
RASGRP4 (HGNC:18958): (RAS guanyl releasing protein 4) The protein encoded by this gene is a member of the Ras guanyl nucleotide-releasing protein (RasGRP) family of Ras guanine nucleotide exchange factors. It contains a Ras exchange motif, a diacylglycerol-binding domain, and two calcium-binding EF hands. This protein was shown to activate H-Ras in a cation-dependent manner in vitro. Expression of this protein in myeloid cell lines was found to be correlated with elevated level of activated RAS protein, and the RAS activation can be greatly enhanced by phorbol ester treatment, which suggested a role of this protein in diacylglycerol regulated cell signaling pathways. Studies of a mast cell leukemia cell line expressing substantial amounts of abnormal transcripts of this gene indicated that this gene may play an important role in the final stages of mast cell development. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RASGRP4 | ENST00000615439.5 | c.1490A>T | p.Asn497Ile | missense_variant | Exon 12 of 17 | 1 | NM_170604.3 | ENSP00000479844.1 | ||
RASGRP4 | ENST00000587738.2 | c.1490A>T | p.Asn497Ile | missense_variant | Exon 12 of 17 | 5 | ENSP00000465772.1 | |||
RASGRP4 | ENST00000586305.5 | c.1448A>T | p.Asn483Ile | missense_variant | Exon 12 of 17 | 1 | ENSP00000467604.1 | |||
RASGRP4 | ENST00000454404.6 | c.1388A>T | p.Asn463Ile | missense_variant | Exon 12 of 17 | 1 | ENSP00000416463.2 | |||
RASGRP4 | ENST00000587753.5 | c.1283A>T | p.Asn428Ile | missense_variant | Exon 12 of 17 | 1 | ENSP00000468483.1 | |||
RASGRP4 | ENST00000614135.4 | c.1214A>T | p.Asn405Ile | missense_variant | Exon 11 of 16 | 5 | ENSP00000479078.1 | |||
RASGRP4 | ENST00000617966.4 | c.1199A>T | p.Asn400Ile | missense_variant | Exon 10 of 15 | 5 | ENSP00000479888.1 | |||
RASGRP4 | ENST00000622174.4 | c.923A>T | p.Asn308Ile | missense_variant | Exon 9 of 14 | 5 | ENSP00000484345.1 | |||
RASGRP4 | ENST00000589358.5 | n.1490A>T | non_coding_transcript_exon_variant | Exon 12 of 18 | 5 | ENSP00000465742.1 | ||||
RASGRP4 | ENST00000589474.5 | n.1448A>T | non_coding_transcript_exon_variant | Exon 12 of 18 | 5 | ENSP00000466928.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
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
Uncertain
.;.;.;D;D;.;D;D;D;D;D;.
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;.;.;.;.;.;.;.;L;.;L
PrimateAI
Benign
T
PROVEAN
Pathogenic
.;.;.;.;.;.;.;D;D;.;D;.
REVEL
Benign
Sift
Benign
.;.;.;.;.;.;.;D;D;.;D;.
Sift4G
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D
Polyphen
D;.;.;.;.;.;.;.;.;D;.;D
Vest4
MutPred
0.53
.;.;.;.;.;.;Loss of catalytic residue at N497 (P = 0.002);.;.;Loss of catalytic residue at N497 (P = 0.002);.;Loss of catalytic residue at N497 (P = 0.002);
MVP
MPC
0.94
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at