2-33527232-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001139488.2(RASGRP3):c.903C>A(p.Ile301=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00463 in 1,614,048 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (20 hom.)
• Consequence: RASGRP3 NM_001139488.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.108

Genes affected

RASGRP3 (HGNC:14545): (RAS guanyl releasing protein 3) The protein encoded by this gene is a guanine nucleotide exchange factor that activates the oncogenes HRAS and RAP1A. Defects in this gene have been associated with systemic lupus erythematosus and several cancers. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 2-33527232-C-A is Benign according to our data. Variant chr2-33527232-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2650821.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASGRP3	NM_001139488.2	c.903C>A	p.Ile301=	synonymous_variant	10/18	ENST00000403687.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASGRP3	ENST00000403687.8	c.903C>A	p.Ile301=	synonymous_variant	10/18	1	NM_001139488.2	P5

Frequencies

GnomAD3 genomes AF: 0.00314 AC: 478 AN: 152242 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00553

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00301 AC: 751 AN: 249170 Hom.: 2 AF XY: 0.00311 AC XY: 421 AN XY: 135176

Gnomad AFR exome AF: 0.000840

Gnomad AMR exome AF: 0.00122

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.000789

Gnomad NFE exome AF: 0.00576

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.00479 AC: 7001 AN: 1461688 Hom.: 20 Cov.: 32 AF XY: 0.00466 AC XY: 3387 AN XY: 727124

Gnomad4 AFR exome AF: 0.000926

Gnomad4 AMR exome AF: 0.00134

Gnomad4 ASJ exome AF: 0.00145

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.00109

Gnomad4 NFE exome AF: 0.00595

Gnomad4 OTH exome AF: 0.00288

GnomAD4 genome AF: 0.00314 AC: 478 AN: 152360 Hom.: 1 Cov.: 32 AF XY: 0.00256 AC XY: 191 AN XY: 74510

Gnomad4 AFR AF: 0.00111

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00553

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00496 Hom.: 1

Bravo AF: 0.00298

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00431

EpiControl AF: 0.00462

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

RASGRP3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	13
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs34636269; hg19: chr2-33752299; COSMIC: COSV67822423; COSMIC: COSV67822423;