2-33476823-T-C

Position:

• chr2-33476823-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+116T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0635 in 145,782 control chromosomes in the GnomAD database, including 382 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 0.064 (382 hom., cov: 30)
  • Exomes 𝑓: 0.014 (0 hom.)
• Consequence: RASGRP3 NM_001139488.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.700

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASGRP3	NM_001139488.2	c.-261+116T>C		intron_variant		ENST00000403687.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASGRP3	ENST00000403687.8	c.-261+116T>C		intron_variant		1	NM_001139488.2	P5

Frequencies

GnomAD3 genomes AF: 0.0636 AC: 9245 AN: 145334 Hom.: 380 Cov.: 30

Gnomad AFR AF: 0.0624

Gnomad AMI AF: 0.0586

Gnomad AMR AF: 0.0453

Gnomad ASJ AF: 0.0191

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.0535

Gnomad FIN AF: 0.0408

Gnomad MID AF: 0.0298

Gnomad NFE AF: 0.0677

Gnomad OTH AF: 0.0590

GnomAD4 exome AF: 0.0138 AC: 5 AN: 362 Hom.: 0 AF XY: 0.0112 AC XY: 3 AN XY: 268

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0625

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0131

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0636 AC: 9252 AN: 145420 Hom.: 382 Cov.: 30 AF XY: 0.0609 AC XY: 4323 AN XY: 70990

Gnomad4 AFR AF: 0.0625

Gnomad4 AMR AF: 0.0454

Gnomad4 ASJ AF: 0.0191

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.0534

Gnomad4 FIN AF: 0.0408

Gnomad4 NFE AF: 0.0677

Gnomad4 OTH AF: 0.0579

Alfa AF: 0.0665 Hom.: 769

Bravo AF: 0.0616

Asia WGS AF: 0.0970 AC: 336 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.3
DANN	Benign	0.67

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: rs13385731; hg19: chr2-33701890;