rs776295355

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.1715G>T(p.Arg572Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000005 in 1,601,168 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RASGRP4
NM_170604.3 missense, splice_region

Scores

Splicing: ADA: 0.0003972

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.161

Variant links:

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]

RASGRP4 links:

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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

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGRP4	NM_170604.3 link	c.1715G>T	p.Arg572Leu	missense_variant, splice_region_variant	Exon 14 of 17	ENST00000615439.5	NP_733749.1	Q8TDF6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RASGRP4	ENST00000615439.5 link	c.1715G>T	p.Arg572Leu	missense_variant, splice_region_variant	Exon 14 of 17	1	NM_170604.3	ENSP00000479844.1	Q8TDF6-1
RASGRP4	ENST00000587738.2 link	c.1715G>T	p.Arg572Leu	missense_variant, splice_region_variant	Exon 14 of 17	5		ENSP00000465772.1	Q8TDF6-1
RASGRP4	ENST00000586305.5 link	c.1673G>T	p.Arg558Leu	missense_variant, splice_region_variant	Exon 14 of 17	1		ENSP00000467604.1	Q8TDF6-2
RASGRP4	ENST00000454404.6 link	c.1613G>T	p.Arg538Leu	missense_variant, splice_region_variant	Exon 14 of 17	1		ENSP00000416463.2	Q8TDF6-8
RASGRP4	ENST00000587753.5 link	c.1508G>T	p.Arg503Leu	missense_variant, splice_region_variant	Exon 14 of 17	1		ENSP00000468483.1	Q8TDF6-9
RASGRP4	ENST00000614135.4 link	c.1439G>T	p.Arg480Leu	missense_variant, splice_region_variant	Exon 13 of 16	5		ENSP00000479078.1	Q8TDF6-5
RASGRP4	ENST00000617966.4 link	c.1424G>T	p.Arg475Leu	missense_variant, splice_region_variant	Exon 12 of 15	5		ENSP00000479888.1	Q8TDF6-7
RASGRP4	ENST00000622174.4 link	c.1148G>T	p.Arg383Leu	missense_variant, splice_region_variant	Exon 11 of 14	5		ENSP00000484345.1	Q8TDF6-6
RASGRP4	ENST00000589358.5 link	n.1715G>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 14 of 18	5		ENSP00000465742.1	Q8TDF6-1
RASGRP4	ENST00000589474.5 link	n.1673G>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 14 of 18	5		ENSP00000466928.1	Q8TDF6-2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000875

AC:

AN:

228476

Hom.:

AF XY:

0.00000808

AC XY:

AN XY:

123764

show subpopulations

Gnomad AFR exome

AF:

0.0000749

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000974

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1448998

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

719532

show subpopulations

Gnomad4 AFR exome

AF:

0.0000603

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:

9.04e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000642

ExAC

AF:

0.0000166

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

.;.;.;.;.;.;T;.;.;D;.;D

Eigen

Benign

0.054

Eigen_PC

Benign

0.086

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.90

.;.;.;D;D;.;T;D;D;D;D;.

M_CAP

Pathogenic

0.31

MetaRNN

Uncertain

0.64

D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.54

MutationAssessor

Benign

1.2

.;.;.;.;.;.;.;.;.;L;.;L

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-4.8

.;.;.;.;.;.;.;D;D;.;D;.

REVEL

Uncertain

0.51

Sift

Uncertain

0.012

.;.;.;.;.;.;.;D;D;.;D;.

Sift4G

Uncertain

0.027

D;D;T;D;D;D;D;D;D;D;T;D

Polyphen

0.25

B;.;.;.;.;.;.;.;.;P;.;P

Vest4

0.48

MutPred

0.29

.;.;.;.;.;.;Loss of disorder (P = 0.0506);.;.;Loss of disorder (P = 0.0506);.;Loss of disorder (P = 0.0506);

MVP

0.83

MPC

0.87

ClinPred

0.60

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.40

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00040

dbscSNV1_RF

Benign

0.28

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over