rs5030975

Variant names:

• chr3-49887514-G-A
• rs5030975
• NM_002447.4:c.3996C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002447.4(MST1R):​c.3996C>T​(p.Pro1332Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00727 in 1,614,174 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0076 (69 hom.)
• Consequence: MST1R NM_002447.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0270
• Publications: 2 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 3-49887514-G-A is Benign according to our data. Variant chr3-49887514-G-A is described in ClinVar as [Benign]. Clinvar id is 708319.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.027 with no splicing effect.
• BS2: High AC in GnomAd4 at 672 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MST1R	NM_002447.4	c.3996C>T	p.Pro1332Pro	synonymous_variant	Exon 20 of 20	ENST00000296474.8	NP_002438.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MST1R	ENST00000296474.8	c.3996C>T	p.Pro1332Pro	synonymous_variant	Exon 20 of 20	1	NM_002447.4	ENSP00000296474.3

Frequencies

GnomAD3 genomes AF: 0.00441 AC: 672 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00754

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00372 AC: 935 AN: 251124 AF XY: 0.00359

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.00226

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.00708

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00756 AC: 11058 AN: 1461832 Hom.: 69 Cov.: 34 AF XY: 0.00718 AC XY: 5225 AN XY: 727212

African (AFR) AF: 0.00117 AC: 39 AN: 33476

American (AMR) AF: 0.00217 AC: 97 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00157 AC: 41 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86258

European-Finnish (FIN) AF: 0.000524 AC: 28 AN: 53398

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00944 AC: 10496 AN: 1111986

Other (OTH) AF: 0.00571 AC: 345 AN: 60392

GnomAD4 genome AF: 0.00441 AC: 672 AN: 152342 Hom.: 0 Cov.: 33 AF XY: 0.00401 AC XY: 299 AN XY: 74510

African (AFR) AF: 0.00173 AC: 72 AN: 41590

American (AMR) AF: 0.00314 AC: 48 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10624

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00754 AC: 513 AN: 68028

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00512 Hom.: 2

Bravo AF: 0.00408

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	1.2
DANN	Benign	0.31
PhyloP100		-0.027
Mutation Taster		=82/18	polymorphism

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: rs5030975; hg19: chr3-49924947; COSMIC: COSV56574273;