rs10215153

chr7-116759077-G-A

Variant summary

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

The NM_000245.4(MET):c.2265-314G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,916 control chromosomes in the GnomAD database, including 7,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (7802 hom., cov: 33)
• Consequence: MET NM_000245.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.14

Genes affected

MET (HGNC:7029): (MET proto-oncogene, receptor tyrosine kinase) This gene encodes a member of the receptor tyrosine kinase family of proteins and the product of the proto-oncogene MET. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that are linked via disulfide bonds to form the mature receptor. Further processing of the beta subunit results in the formation of the M10 peptide, which has been shown to reduce lung fibrosis. Binding of its ligand, hepatocyte growth factor, induces dimerization and activation of the receptor, which plays a role in cellular survival, embryogenesis, and cellular migration and invasion. Mutations in this gene are associated with papillary renal cell carcinoma, hepatocellular carcinoma, and various head and neck cancers. Amplification and overexpression of this gene are also associated with multiple human cancers. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-116759077-G-A is Benign according to our data. Variant chr7-116759077-G-A is described in ClinVar as [Benign]. Clinvar id is 1183625.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MET	NM_000245.4	c.2265-314G>A		intron_variant		ENST00000397752.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MET	ENST00000397752.8	c.2265-314G>A		intron_variant		1	NM_000245.4	P3
MET	ENST00000318493.11	c.2265-260G>A		intron_variant		1		A2
MET	ENST00000436117.3	c.2264+457G>A		intron_variant, NMD_transcript_variant		1
MET	ENST00000422097.2	c.2265-314G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47482 AN: 151798 Hom.: 7796 Cov.: 33

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.340

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.313 AC: 47530 AN: 151916 Hom.: 7802 Cov.: 33 AF XY: 0.308 AC XY: 22848 AN XY: 74246

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.0999

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.312

Alfa AF: 0.310 Hom.: 10111

Bravo AF: 0.317

Asia WGS AF: 0.137 AC: 478 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.0040
Dann	Benign	0.53

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: rs10215153; hg19: chr7-116399131; COSMIC: COSV100577600; COSMIC: COSV100577600;