Genetic Variant NM_002447.4:c.3811-10C>A (chr3-49890070-G-T) – ACMG Classification: Benign (-13 pts)

Variant summary

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

The NM_002447.4(MST1R):c.3811-10C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0755 in 1,589,556 control chromosomes in the GnomAD database, including 4,798 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.074 ( 444 hom., cov: 32)

Exomes 𝑓: 0.076 ( 4354 hom. )

Consequence

MST1R
NM_002447.4 intron

Scores

Splicing: ADA: 0.003578

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0650

Publications

19 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:

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 (BayesDel_noAF=-0.8).

BP6

Variant 3-49890070-G-T is Benign according to our data. Variant chr3-49890070-G-T is described in ClinVar as [Benign]. Clinvar id is 3055583.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MST1R	NM_002447.4 link	c.3811-10C>A		intron_variant	Intron 18 of 19	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.3811-10C>A		intron_variant	Intron 18 of 19	1	NM_002447.4	ENSP00000296474.3		Q04912-1

Frequencies

GnomAD3 genomes

AF:

0.0741

AC:

11279

AN:

152154

Hom.:

444

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0888

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.0473

Gnomad ASJ

AF:

0.0709

Gnomad EAS

AF:

0.0250

Gnomad SAS

AF:

0.0565

Gnomad FIN

AF:

0.0673

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0770

Gnomad OTH

AF:

0.0766

GnomAD2 exomes

AF:

0.0625

AC:

14276

AN:

228480

AF XY:

0.0629

show subpopulations

Gnomad AFR exome

AF:

0.0906

Gnomad AMR exome

AF:

0.0330

Gnomad ASJ exome

AF:

0.0674

Gnomad EAS exome

AF:

0.0280

Gnomad FIN exome

AF:

0.0694

Gnomad NFE exome

AF:

0.0730

Gnomad OTH exome

AF:

0.0660

GnomAD4 exome

AF:

0.0756

AC:

108701

AN:

1437284

Hom.:

4354

Cov.:

AF XY:

0.0747

AC XY:

53208

AN XY:

712376

show subpopulations

African (AFR)

AF:

0.0863

AC:

2844

AN:

32968

American (AMR)

AF:

0.0350

AC:

1480

AN:

42244

Ashkenazi Jewish (ASJ)

AF:

0.0710

AC:

1718

AN:

24208

East Asian (EAS)

AF:

0.0210

AC:

826

AN:

39426

South Asian (SAS)

AF:

0.0575

AC:

4694

AN:

81650

European-Finnish (FIN)

AF:

0.0679

AC:

3563

AN:

52444

Middle Eastern (MID)

AF:

0.0457

AC:

258

AN:

5646

European-Non Finnish (NFE)

AF:

0.0812

AC:

89227

AN:

1099322

Other (OTH)

AF:

0.0689

AC:

4091

AN:

59376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

5369

10739

16108

21478

26847

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0741

AC:

11285

AN:

152272

Hom.:

444

Cov.:

AF XY:

0.0718

AC XY:

5350

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0887

AC:

3686

AN:

41552

American (AMR)

AF:

0.0472

AC:

722

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0709

AC:

246

AN:

3470

East Asian (EAS)

AF:

0.0245

AC:

127

AN:

5178

South Asian (SAS)

AF:

0.0570

AC:

275

AN:

4828

European-Finnish (FIN)

AF:

0.0673

AC:

715

AN:

10622

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0770

AC:

5237

AN:

68002

Other (OTH)

AF:

0.0777

AC:

164

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

543

1085

1628

2170

2713

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0678

Hom.:

522

Bravo

AF:

0.0737

Asia WGS

AF:

0.0540

AC:

188

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MST1R-related disorder

Benign:1

Dec 16, 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

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.2

(source)

DANN

Benign

0.75

PhyloP100

0.065

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0036

dbscSNV1_RF

Benign

0.11

SpliceAI score (max)

0.050

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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NM_002447.4:c.3811-10C>A

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