3-49889180-C-G

Position:

• chr3-49889180-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002447.4(MST1R):​c.3947+744G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,134 control chromosomes in the GnomAD database, including 9,459 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (9459 hom., cov: 32)
• Consequence: MST1R NM_002447.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MST1R	NM_002447.4	c.3947+744G>C		intron_variant		ENST00000296474.8	NP_002438.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MST1R	ENST00000296474.8	c.3947+744G>C		intron_variant		1	NM_002447.4	ENSP00000296474.3
MST1R	ENST00000621387.4	c.3629+744G>C		intron_variant		1		ENSP00000482642.1
MST1R	ENST00000344206.8	c.3800+744G>C		intron_variant		5		ENSP00000341325.4
MST1R	ENST00000411578.6	n.*769+744G>C		intron_variant		5		ENSP00000407926.2

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51926 AN: 152014 Hom.: 9454 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.359

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.341 AC: 51943 AN: 152134 Hom.: 9459 Cov.: 32 AF XY: 0.331 AC XY: 24641 AN XY: 74374

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.361

Alfa AF: 0.238 Hom.: 565

Bravo AF: 0.344

Asia WGS AF: 0.202 AC: 702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.4
DANN	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs7627864; hg19: chr3-49926613;