rs13408063

Positions:

• chr2-33493188-T-C

Variant summary

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

The NM_001139488.2(RASGRP3):​c.-261+16481T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,076 control chromosomes in the GnomAD database, including 8,756 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 0.33 (8755 hom., cov: 32)
  • Exomes 𝑓: 0.24 (1 hom.)
• Consequence: RASGRP3 NM_001139488.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.717

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 = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASGRP3	NM_001139488.2	c.-261+16481T>C		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+16481T>C		intron_variant		1	NM_001139488.2	ENSP00000384192	P5

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49706 AN: 151924 Hom.: 8727 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.294

GnomAD4 exome AF: 0.235 AC: 8 AN: 34 Hom.: 1 Cov.: 0 AF XY: 0.233 AC XY: 7 AN XY: 30

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.328 AC: 49796 AN: 152042 Hom.: 8755 Cov.: 32 AF XY: 0.331 AC XY: 24634 AN XY: 74328

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.300

Alfa AF: 0.280 Hom.: 8294

Bravo AF: 0.335

Asia WGS AF: 0.377 AC: 1309 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	0.49
DANN	Benign	0.44

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: rs13408063; hg19: chr2-33718255;