2-33457670-G-T

Variant names:

• chr2-33457670-G-T
• rs2124437
• ENST00000402538.8:c.-261+9727G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000402538.8(RASGRP3):​c.-261+9727G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 151,704 control chromosomes in the GnomAD database, including 32,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: 𝑓 0.66 (32872 hom., cov: 29)
• Consequence: RASGRP3 ENST00000402538.8 intron
• Clinical Significance: - - O:1
• Conservation: PhyloP100: 0.150
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGRP3	NM_001349975.2	c.-383+9727G>T		intron_variant	Intron 2 of 19		NP_001336904.1
RASGRP3	NM_170672.3	c.-261+9727G>T		intron_variant	Intron 2 of 18		NP_733772.1
RASGRP3	NM_001349978.2	c.-261+9727G>T		intron_variant	Intron 2 of 18		NP_001336907.1
RASGRP3	XM_011532746.4	c.-159+9727G>T		intron_variant	Intron 2 of 18		XP_011531048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGRP3	ENST00000402538.8	c.-261+9727G>T		intron_variant	Intron 2 of 18	1		ENSP00000385886.3
RASGRP3	ENST00000479528.5	n.149+9727G>T		intron_variant	Intron 2 of 4	3
RASGRP3	ENST00000484909.5	n.390+9727G>T		intron_variant	Intron 2 of 2	2
RASGRP3	ENST00000497723.6	n.303+9727G>T		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99418 AN: 151586 Hom.: 32872 Cov.: 29

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.708

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.680

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.656 AC: 99458 AN: 151704 Hom.: 32872 Cov.: 29 AF XY: 0.656 AC XY: 48599 AN XY: 74114

African (AFR) AF: 0.658 AC: 27212 AN: 41354

American (AMR) AF: 0.636 AC: 9682 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2207 AN: 3468

East Asian (EAS) AF: 0.678 AC: 3499 AN: 5164

South Asian (SAS) AF: 0.546 AC: 2625 AN: 4806

European-Finnish (FIN) AF: 0.742 AC: 7799 AN: 10506

Middle Eastern (MID) AF: 0.710 AC: 206 AN: 290

European-Non Finnish (NFE) AF: 0.651 AC: 44223 AN: 67890

Other (OTH) AF: 0.676 AC: 1418 AN: 2098

Alfa AF: 0.644 Hom.: 18458

Bravo AF: 0.650

Asia WGS AF: 0.593 AC: 2062 AN: 3478

ClinVar

Significance: -

Submissions summary: Other:1

Revision: -

Submissions by phenotype

Lip and oral cavity carcinoma Other:1

Nov 02, 2015

Department of Biological Science, Sunandan Divatia School of Science, NMIMS University

Significance: association

Review Status: criteria provided, single submitter

Collection Method: case-control

The frequency of the homozygous SNP genotypes were observed more in the oral cancer patients in comparison to controls, implying the role of this genotype in predisposition of oral cancer. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.9
DANN	Benign	0.73
PhyloP100		0.15
PromoterAI		-0.00080	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs2124437; hg19: chr2-33682737;