chr3-49887507-T-C

Variant names:

• chr3-49887507-T-C
• rs1062633
• NM_002447.4:c.4003A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -3.17
• Publications: 67 publications found

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)

ENSG00000295244 (HGNC:):

ACMG classification

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002447.4. 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
	MST1R	NM_002447.4	MANE Select	c.4003A>G	p.Arg1335Gly	missense	Exon 20 of 20	NP_002438.2	Q04912-1
	MST1R	NM_001244937.3		c.3856A>G	p.Arg1286Gly	missense	Exon 19 of 19	NP_001231866.1	Q04912-2
	MST1R	NM_001437543.1		c.3796A>G	p.Arg1266Gly	missense	Exon 19 of 19	NP_001424472.1	H7C074

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MST1R	ENST00000296474.8	TSL:1 MANE Select	c.4003A>G	p.Arg1335Gly	missense	Exon 20 of 20	ENSP00000296474.3	Q04912-1
	MST1R	ENST00000621387.4	TSL:1	c.3685A>G	p.Arg1229Gly	missense	Exon 18 of 18	ENSP00000482642.1	Q04912-7
	MST1R	ENST00000858906.1		c.4006A>G	p.Arg1336Gly	missense	Exon 21 of 21	ENSP00000528965.1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77240 AN: 151986 Hom.: 21084 Cov.: 33

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

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.: 55 AF XY: 0.468 AC XY: 340628 AN XY: 727178

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

GnomAD4 genome AF: 0.508 AC: 77320 AN: 152104 Hom.: 21115 Cov.: 33 AF XY: 0.493 AC XY: 36679 AN XY: 74360

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

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

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MST1R-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.041
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.020
DANN	Benign	0.16
DEOGEN2	Benign	0.16	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.0000035	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.90	L
PhyloP100		-3.2
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.11
Sift	Benign	0.51	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.057
MPC		0.23
ClinPred		0.0060	T
GERP RS		-4.2
Varity_R		0.17
gMVP		0.46
Mutation Taster		=92/8	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: rs1062633; hg19: chr3-49924940; COSMIC: COSV56566222; COSMIC: COSV56566222;