6-159907588-C-T

Variant names:

• chr6-159907588-C-T
• rs220721
• NM_002377.4:c.633C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002377.4(MAS1):​c.633C>T​(p.Val211Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,613,488 control chromosomes in the GnomAD database, including 54,798 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 0.27 (6397 hom., cov: 30)
  • Exomes 𝑓: 0.24 (48401 hom.)
• Consequence: MAS1 NM_002377.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.593
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=-0.593 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002377.4. 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
	MAS1	NM_002377.4	MANE Select	c.633C>T	p.Val211Val	synonymous	Exon 3 of 3	NP_002368.1	P04201
	MAS1	NM_001366704.2		c.633C>T	p.Val211Val	synonymous	Exon 2 of 2	NP_001353633.1	P04201

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAS1	ENST00000674077.2	MANE Select	c.633C>T	p.Val211Val	synonymous	Exon 3 of 3	ENSP00000501180.2	P04201
	MAS1	ENST00000252660.5	TSL:6	c.633C>T	p.Val211Val	synonymous	Exon 1 of 1	ENSP00000252660.4	P04201

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41657 AN: 151568 Hom.: 6396 Cov.: 30

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.255

GnomAD2 exomes AF: 0.291 AC: 73071 AN: 251154 AF XY: 0.278

Gnomad AFR exome AF: 0.285

Gnomad AMR exome AF: 0.400

Gnomad ASJ exome AF: 0.185

Gnomad EAS exome AF: 0.661

Gnomad FIN exome AF: 0.358

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.265

GnomAD4 exome AF: 0.241 AC: 352460 AN: 1461802 Hom.: 48401 Cov.: 35 AF XY: 0.238 AC XY: 173253 AN XY: 727200

African (AFR) AF: 0.282 AC: 9439 AN: 33480

American (AMR) AF: 0.385 AC: 17213 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 4984 AN: 26136

East Asian (EAS) AF: 0.678 AC: 26908 AN: 39700

South Asian (SAS) AF: 0.188 AC: 16258 AN: 86250

European-Finnish (FIN) AF: 0.354 AC: 18893 AN: 53386

Middle Eastern (MID) AF: 0.211 AC: 1215 AN: 5768

European-Non Finnish (NFE) AF: 0.218 AC: 242541 AN: 1111970

Other (OTH) AF: 0.249 AC: 15009 AN: 60390

GnomAD4 genome AF: 0.275 AC: 41678 AN: 151686 Hom.: 6397 Cov.: 30 AF XY: 0.285 AC XY: 21082 AN XY: 74086

African (AFR) AF: 0.283 AC: 11696 AN: 41368

American (AMR) AF: 0.322 AC: 4897 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 665 AN: 3464

East Asian (EAS) AF: 0.657 AC: 3352 AN: 5104

South Asian (SAS) AF: 0.192 AC: 919 AN: 4786

European-Finnish (FIN) AF: 0.362 AC: 3814 AN: 10522

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15455 AN: 67910

Other (OTH) AF: 0.258 AC: 542 AN: 2100

Alfa AF: 0.241 Hom.: 8575

Bravo AF: 0.277

Asia WGS AF: 0.400 AC: 1389 AN: 3478

EpiCase AF: 0.218

EpiControl AF: 0.213

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.3
DANN	Benign	0.55
PhyloP100		-0.59
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: rs220721; hg19: chr6-160328620; COSMIC: COSV53120684;