chr2-33522003-C-T

Variant names:

• chr2-33522003-C-T
• rs189837410
• NM_001139488.2:c.417C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001139488.2(RASGRP3):​c.417C>T​(p.Ser139Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000368 in 1,613,834 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00020 (2 hom.)
• Consequence: RASGRP3 NM_001139488.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.944
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 2-33522003-C-T is Benign according to our data. Variant chr2-33522003-C-T is described in ClinVar as Benign. ClinVar VariationId is 783973.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.944 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 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.417C>T	p.Ser139Ser	synonymous	Exon 7 of 18	NP_001132960.1	Q8IV61-1
	RASGRP3	NM_001349975.2		c.417C>T	p.Ser139Ser	synonymous	Exon 9 of 20	NP_001336904.1	Q8IV61-1
	RASGRP3	NM_001349976.2		c.417C>T	p.Ser139Ser	synonymous	Exon 7 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.417C>T	p.Ser139Ser	synonymous	Exon 7 of 18	ENSP00000384192.3	Q8IV61-1
	RASGRP3	ENST00000402538.8	TSL:1	c.417C>T	p.Ser139Ser	synonymous	Exon 8 of 19	ENSP00000385886.3	Q8IV61-1
	RASGRP3	ENST00000407811.5	TSL:1	c.417C>T	p.Ser139Ser	synonymous	Exon 6 of 17	ENSP00000383917.1	Q8IV61-2

Frequencies

GnomAD3 genomes AF: 0.00197 AC: 300 AN: 152158 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00678

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000502 AC: 125 AN: 248868 AF XY: 0.000400

Gnomad AFR exome AF: 0.00743

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000201 AC: 294 AN: 1461558 Hom.: 2 Cov.: 30 AF XY: 0.000161 AC XY: 117 AN XY: 727046

African (AFR) AF: 0.00747 AC: 250 AN: 33474

American (AMR) AF: 0.000313 AC: 14 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39688

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111796

Other (OTH) AF: 0.000398 AC: 24 AN: 60372

GnomAD4 genome AF: 0.00197 AC: 300 AN: 152276 Hom.: 1 Cov.: 33 AF XY: 0.00199 AC XY: 148 AN XY: 74462

African (AFR) AF: 0.00676 AC: 281 AN: 41550

American (AMR) AF: 0.000981 AC: 15 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00111 Hom.: 0

Bravo AF: 0.00237

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.49
CADD	Benign	5.3
DANN	Benign	0.75
PhyloP100		-0.94
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs189837410; hg19: chr2-33747070;