Variant chr19-38412690-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_170604.3(RASGRP4):c.1662C>T(p.Cys554=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00884 in 1,613,282 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0062 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0091 ( 77 hom. )

Consequence

RASGRP4
NM_170604.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.103

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 Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 19-38412690-G-A is Benign according to our data. Variant chr19-38412690-G-A is described in ClinVar as [Benign]. Clinvar id is 774958.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.103 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASGRP4	NM_170604.3 linkuse as main transcript	c.1662C>T	p.Cys554=	synonymous_variant	13/17	ENST00000615439.5	NP_733749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASGRP4	ENST00000615439.5 linkuse as main transcript	c.1662C>T	p.Cys554=	synonymous_variant	13/17	1	NM_170604.3	ENSP00000479844	P1	Q8TDF6-1

Frequencies

GnomAD3 genomes

AF:

0.00617

AC:

939

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0120

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00938

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00566

AC:

1402

AN:

247738

Hom.:

AF XY:

0.00583

AC XY:

783

AN XY:

134400

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.00181

Gnomad ASJ exome

AF:

0.00320

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00342

Gnomad FIN exome

AF:

0.00975

Gnomad NFE exome

AF:

0.00839

Gnomad OTH exome

AF:

0.00565

GnomAD4 exome

AF:

0.00912

AC:

13330

AN:

1460988

Hom.:

Cov.:

AF XY:

0.00904

AC XY:

6573

AN XY:

726714

show subpopulations

Gnomad4 AFR exome

AF:

0.00155

Gnomad4 AMR exome

AF:

0.00175

Gnomad4 ASJ exome

AF:

0.00284

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00282

Gnomad4 FIN exome

AF:

0.0104

Gnomad4 NFE exome

AF:

0.0107

Gnomad4 OTH exome

AF:

0.00787

GnomAD4 genome

AF:

0.00617

AC:

939

AN:

152294

Hom.:

Cov.:

AF XY:

0.00599

AC XY:

446

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00202

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0120

Gnomad4 NFE

AF:

0.00938

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00762

Hom.:

Bravo

AF:

0.00533

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.3

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over