rs34636269

Variant names:

• chr2-33527232-C-A
• rs34636269
• NM_001139488.2:c.903C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-33527232-C-A
• chr2-33527232-C-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001139488.2(RASGRP3):​c.903C>A​(p.Ile301Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00463 in 1,614,048 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (20 hom.)
• Consequence: RASGRP3 NM_001139488.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.108
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 2-33527232-C-A is Benign according to our data. Variant chr2-33527232-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2650821.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 20 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001139488.2. 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_001139488.2	MANE Select	c.903C>A	p.Ile301Ile	synonymous	Exon 10 of 18	NP_001132960.1	Q8IV61-1
	RASGRP3	NM_001349975.2		c.903C>A	p.Ile301Ile	synonymous	Exon 12 of 20	NP_001336904.1	Q8IV61-1
	RASGRP3	NM_001349976.2		c.903C>A	p.Ile301Ile	synonymous	Exon 10 of 18	NP_001336905.1	Q8IV61-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGRP3	ENST00000403687.8	TSL:1 MANE Select	c.903C>A	p.Ile301Ile	synonymous	Exon 10 of 18	ENSP00000384192.3	Q8IV61-1
	RASGRP3	ENST00000402538.8	TSL:1	c.903C>A	p.Ile301Ile	synonymous	Exon 11 of 19	ENSP00000385886.3	Q8IV61-1
	RASGRP3	ENST00000407811.5	TSL:1	c.903C>A	p.Ile301Ile	synonymous	Exon 9 of 17	ENSP00000383917.1	Q8IV61-2

Frequencies

GnomAD3 genomes AF: 0.00314 AC: 478 AN: 152242 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00553

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00301 AC: 751 AN: 249170 AF XY: 0.00311

Gnomad AFR exome AF: 0.000840

Gnomad AMR exome AF: 0.00122

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000789

Gnomad NFE exome AF: 0.00576

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.00479 AC: 7001 AN: 1461688 Hom.: 20 Cov.: 32 AF XY: 0.00466 AC XY: 3387 AN XY: 727124

African (AFR) AF: 0.000926 AC: 31 AN: 33480

American (AMR) AF: 0.00134 AC: 60 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00145 AC: 38 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86254

European-Finnish (FIN) AF: 0.00109 AC: 58 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00595 AC: 6620 AN: 1111850

Other (OTH) AF: 0.00288 AC: 174 AN: 60374

GnomAD4 genome AF: 0.00314 AC: 478 AN: 152360 Hom.: 1 Cov.: 32 AF XY: 0.00256 AC XY: 191 AN XY: 74510

African (AFR) AF: 0.00111 AC: 46 AN: 41580

American (AMR) AF: 0.00157 AC: 24 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00553 AC: 376 AN: 68030

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00496 Hom.: 1

Bravo AF: 0.00298

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00431

EpiControl AF: 0.00462

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	13
DANN	Benign	0.78
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs34636269; hg19: chr2-33752299; COSMIC: COSV67822423; COSMIC: COSV67822423;