rs220721

Positions:

• chr6-159907588-C-A
• chr6-159907588-C-G
• chr6-159907588-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002377.4(MAS1):​c.633C>A​(p.Val211Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
• Consequence: MAS1 NM_002377.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.593

Genes affected

MAS1 (HGNC:6899): (MAS1 proto-oncogene, G protein-coupled receptor) This gene encodes a class I seven-transmembrane G-protein-coupled receptor. The encoded protein is a receptor for angiotensin-(1-7) and preferentially couples to the Gq protein, activating the phospholipase C signaling pathway. The encoded protein may play a role in multiple processes including hypotension, smooth muscle relaxation and cardioprotection by mediating the effects of angiotensin-(1-7). [provided by RefSeq, May 2012]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-0.593 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAS1	NM_002377.4	c.633C>A	p.Val211Val	synonymous_variant	3/3	ENST00000674077.2	NP_002368.1
MAS1	NM_001366704.2	c.633C>A	p.Val211Val	synonymous_variant	2/2		NP_001353633.1
MAS1	XM_047418776.1	c.633C>A	p.Val211Val	synonymous_variant	4/4		XP_047274732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAS1	ENST00000674077.2	c.633C>A	p.Val211Val	synonymous_variant	3/3		NM_002377.4	ENSP00000501180.2
MAS1	ENST00000252660.5	c.633C>A	p.Val211Val	synonymous_variant	1/1	6		ENSP00000252660.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.44
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs220721; hg19: chr6-160328620; COSMIC: COSV53121865;