rs13385731

Variant names:

• chr2-33476823-T-C
• rs13385731
• NM_001139488.2:c.-261+116T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 63 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=-0.8).
• 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 rank	MANE	Protein	UniProt
RASGRP3	NM_001139488.2	c.-261+116T>C		intron_variant	Intron 1 of 17	ENST00000403687.8	NP_001132960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGRP3	ENST00000403687.8	c.-261+116T>C		intron_variant	Intron 1 of 17	1	NM_001139488.2	ENSP00000384192.3

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

African (AFR) AF: 0.00 AC: 0 AN: 8

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.0625 AC: 1 AN: 16

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.0131 AC: 4 AN: 306

Other (OTH) AF: 0.00 AC: 0 AN: 12

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

African (AFR) AF: 0.0625 AC: 2328 AN: 37232

American (AMR) AF: 0.0454 AC: 665 AN: 14648

Ashkenazi Jewish (ASJ) AF: 0.0191 AC: 65 AN: 3396

East Asian (EAS) AF: 0.160 AC: 816 AN: 5110

South Asian (SAS) AF: 0.0534 AC: 240 AN: 4498

European-Finnish (FIN) AF: 0.0408 AC: 418 AN: 10254

Middle Eastern (MID) AF: 0.0319 AC: 9 AN: 282

European-Non Finnish (NFE) AF: 0.0677 AC: 4543 AN: 67108

Other (OTH) AF: 0.0579 AC: 116 AN: 2004

Alfa AF: 0.0681 Hom.: 1474

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
PhyloP100		0.70
PromoterAI		0.31	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: rs13385731; hg19: chr2-33701890;