3-49890070-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002447.4(MST1R):c.3811-10C>A variant causes a splice polypyrimidine tract, 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 (★).

• Frequency:
  • Genomes: 𝑓 0.074 (444 hom., cov: 32)
  • Exomes 𝑓: 0.076 (4354 hom.)
• Consequence: MST1R NM_002447.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.003578
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0650

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]

ACMG classification

Verdict is Benign. Variant got -14 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 criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
MST1R	NM_002447.4	c.3811-10C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000296474.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MST1R	ENST00000296474.8	c.3811-10C>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002447.4	P2

Frequencies

GnomAD3 genomes AF: 0.0741 AC: 11279 AN: 152154 Hom.: 444 Cov.: 32

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

GnomAD3 exomes AF: 0.0625 AC: 14276 AN: 228480 Hom.: 489 AF XY: 0.0629 AC XY: 7693 AN XY: 122380

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 SAS exome AF: 0.0557

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.: 32 AF XY: 0.0747 AC XY: 53208 AN XY: 712376

Gnomad4 AFR exome AF: 0.0863

Gnomad4 AMR exome AF: 0.0350

Gnomad4 ASJ exome AF: 0.0710

Gnomad4 EAS exome AF: 0.0210

Gnomad4 SAS exome AF: 0.0575

Gnomad4 FIN exome AF: 0.0679

Gnomad4 NFE exome AF: 0.0812

Gnomad4 OTH exome AF: 0.0689

GnomAD4 genome AF: 0.0741 AC: 11285 AN: 152272 Hom.: 444 Cov.: 32 AF XY: 0.0718 AC XY: 5350 AN XY: 74466

Gnomad4 AFR AF: 0.0887

Gnomad4 AMR AF: 0.0472

Gnomad4 ASJ AF: 0.0709

Gnomad4 EAS AF: 0.0245

Gnomad4 SAS AF: 0.0570

Gnomad4 FIN AF: 0.0673

Gnomad4 NFE AF: 0.0770

Gnomad4 OTH AF: 0.0777

Alfa AF: 0.0664 Hom.: 419

Bravo AF: 0.0737

Asia WGS AF: 0.0540 AC: 188 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MST1R-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 16, 2019

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
Dann	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs12489386; hg19: chr3-49927503;