Genetic Variant NM_002377.4:c.633C>T (chr6-159907588-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.593

Publications

20 publications found

Variant links:

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]

MAS1 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAS1	NM_002377.4 link	c.633C>T	p.Val211Val	synonymous_variant	Exon 3 of 3	ENST00000674077.2	NP_002368.1	P04201W8W3P4
MAS1	NM_001366704.2 link	c.633C>T	p.Val211Val	synonymous_variant	Exon 2 of 2		NP_001353633.1
MAS1	XM_047418776.1 link	c.633C>T	p.Val211Val	synonymous_variant	Exon 4 of 4		XP_047274732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAS1	ENST00000674077.2 link	c.633C>T	p.Val211Val	synonymous_variant	Exon 3 of 3		NM_002377.4	ENSP00000501180.2		P04201
MAS1	ENST00000252660.5 link	c.633C>T	p.Val211Val	synonymous_variant	Exon 1 of 1	6		ENSP00000252660.4		P04201

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41657

AN:

151568

Hom.:

6396

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.238

AC XY:

173253

AN XY:

727200

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

15870

31741

47611

63482

79352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8548

17096

25644

34192

42740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.275

AC:

41678

AN:

151686

Hom.:

6397

Cov.:

AF XY:

0.285

AC XY:

21082

AN XY:

74086

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.228

AC:

15455

AN:

67910

Other (OTH)

AF:

0.258

AC:

542

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1446

2892

4339

5785

7231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.3

(source)

DANN

Benign

0.55

PhyloP100

-0.59

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over