2-33492616-G-A

Position:

• chr2-33492616-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001139488.2(RASGRP3):​c.-261+15909G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 151,956 control chromosomes in the GnomAD database, including 13,901 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (13901 hom., cov: 32)
• Consequence: RASGRP3 NM_001139488.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASGRP3	NM_001139488.2	c.-261+15909G>A		intron_variant		ENST00000403687.8	NP_001132960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASGRP3	ENST00000403687.8	c.-261+15909G>A		intron_variant		1	NM_001139488.2	ENSP00000384192	P5

Frequencies

GnomAD3 genomes AF: 0.415 AC: 62985 AN: 151838 Hom.: 13850 Cov.: 32

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.415 AC: 63107 AN: 151956 Hom.: 13901 Cov.: 32 AF XY: 0.417 AC XY: 30991 AN XY: 74276

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.381

Alfa AF: 0.353 Hom.: 8995

Bravo AF: 0.425

Asia WGS AF: 0.403 AC: 1400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.070
DANN	Benign	0.22

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

Publications

LitVar

Other links and lift over

dbSNP: rs13391694; hg19: chr2-33717683;