rs1062633

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_002447.4(MST1R):c.4003A>G(p.Arg1335Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 1,613,852 control chromosomes in the GnomAD database, including 193,380 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.51 ( 21115 hom., cov: 33)

Exomes 𝑓: 0.47 ( 172265 hom. )

Consequence

MST1R
NM_002447.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -3.17

Publications

67 publications found

Variant links:

Genes affected

MST1R (HGNC:7381): (macrophage stimulating 1 receptor) This gene encodes a cell surface receptor for macrophage-stimulating protein (MSP) with tyrosine kinase activity. The mature form of this protein is a heterodimer of disulfide-linked alpha and beta subunits, generated by proteolytic cleavage of a single-chain precursor. The beta subunit undergoes tyrosine phosphorylation upon stimulation by MSP. This protein is expressed on the ciliated epithelia of the mucociliary transport apparatus of the lung, and together with MSP, thought to be involved in host defense. Alternative splicing generates multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Jan 2016]

MST1R Gene-Disease associations (from GenCC):

nasopharyngeal carcinoma, susceptibility to, 3
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

MST1R links:

ENSG00000295244 (HGNC:):

ENSG00000295244 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=3.538798E-6).

BP6

Variant 3-49887507-T-C is Benign according to our data. Variant chr3-49887507-T-C is described in ClinVar as [Benign]. Clinvar id is 3058886.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MST1R	NM_002447.4 link	c.4003A>G	p.Arg1335Gly	missense_variant	Exon 20 of 20	ENST00000296474.8	NP_002438.2	Q04912-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MST1R	ENST00000296474.8 link	c.4003A>G	p.Arg1335Gly	missense_variant	Exon 20 of 20	1	NM_002447.4	ENSP00000296474.3		Q04912-1

Frequencies

GnomAD3 genomes

AF:

0.508

AC:

77240

AN:

151986

Hom.:

21084

Cov.:

show subpopulations

Gnomad AFR

AF:

0.678

Gnomad AMI

AF:

0.535

Gnomad AMR

AF:

0.399

Gnomad ASJ

AF:

0.394

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.384

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.502

Gnomad OTH

AF:

0.500

GnomAD2 exomes

AF:

0.408

AC:

102561

AN:

251134

AF XY:

0.405

show subpopulations

Gnomad AFR exome

AF:

0.686

Gnomad AMR exome

AF:

0.289

Gnomad ASJ exome

AF:

0.402

Gnomad EAS exome

AF:

0.147

Gnomad FIN exome

AF:

0.389

Gnomad NFE exome

AF:

0.497

Gnomad OTH exome

AF:

0.441

GnomAD4 exome

AF:

0.475

AC:

694059

AN:

1461748

Hom.:

172265

Cov.:

AF XY:

0.468

AC XY:

340628

AN XY:

727178

show subpopulations

African (AFR)

AF:

0.683

AC:

22878

AN:

33478

American (AMR)

AF:

0.303

AC:

13557

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.405

AC:

10594

AN:

26136

East Asian (EAS)

AF:

0.153

AC:

6082

AN:

39668

South Asian (SAS)

AF:

0.241

AC:

20780

AN:

86258

European-Finnish (FIN)

AF:

0.390

AC:

20841

AN:

53384

Middle Eastern (MID)

AF:

0.424

AC:

2447

AN:

5768

European-Non Finnish (NFE)

AF:

0.511

AC:

568659

AN:

1111952

Other (OTH)

AF:

0.467

AC:

28221

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

22512

45025

67537

90050

112562

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.508

AC:

77320

AN:

152104

Hom.:

21115

Cov.:

AF XY:

0.493

AC XY:

36679

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.678

AC:

28129

AN:

41498

American (AMR)

AF:

0.398

AC:

6080

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.394

AC:

1367

AN:

3472

East Asian (EAS)

AF:

0.142

AC:

734

AN:

5174

South Asian (SAS)

AF:

0.235

AC:

1133

AN:

4826

European-Finnish (FIN)

AF:

0.384

AC:

4056

AN:

10574

Middle Eastern (MID)

AF:

0.473

AC:

139

AN:

294

European-Non Finnish (NFE)

AF:

0.502

AC:

34131

AN:

67964

Other (OTH)

AF:

0.504

AC:

1064

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1849

3698

5548

7397

9246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.495

Hom.:

74749

Bravo

AF:

0.524

TwinsUK

AF:

0.517

AC:

1917

ALSPAC

AF:

0.519

AC:

2002

ESP6500AA

AF:

0.674

AC:

2969

ESP6500EA

AF:

0.506

AC:

4352

ExAC

AF:

0.417

AC:

50694

Asia WGS

AF:

0.291

AC:

1012

AN:

3478

EpiCase

AF:

0.498

EpiControl

AF:

0.497

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MST1R-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.041

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.020

(source)

DANN

Benign

0.16

DEOGEN2

Benign

0.16

T;.;.;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.13

T;T;T;T;T

MetaRNN

Benign

0.0000035

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.90

L;.;.;.;.

PhyloP100

-3.2

PrimateAI

Benign

0.27

PROVEAN

Benign

0.39

N;.;.;.;N

REVEL

Benign

0.11

Sift

Benign

0.51

T;.;.;.;T

Sift4G

Benign

0.57

T;T;T;T;T

Polyphen

0.0

B;.;.;.;.

Vest4

0.057

MPC

0.23

ClinPred

0.0060

GERP RS

-4.2

Varity_R

0.17

gMVP

0.46

Mutation Taster

=92/8

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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rs1062633

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over