ENST00000402538.8:c.-261+9727G>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: Not reported in ClinVar
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000402538.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGRP3	NM_001349975.2		c.-383+9727G>T		intron	N/A	NP_001336904.1	Q8IV61-1
	RASGRP3	NM_170672.3		c.-261+9727G>T		intron	N/A	NP_733772.1	Q8IV61-1
	RASGRP3	NM_001349978.2		c.-261+9727G>T		intron	N/A	NP_001336907.1	Q8IV61-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGRP3	ENST00000402538.8	TSL:1	c.-261+9727G>T		intron	N/A	ENSP00000385886.3	Q8IV61-1
	RASGRP3	ENST00000967278.1		c.-261+9727G>T		intron	N/A	ENSP00000637337.1
	RASGRP3	ENST00000884676.1		c.-502+9727G>T		intron	N/A	ENSP00000554735.1

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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;