Variant 7-116769637-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_000245.4(MET):c.2584-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MET
NM_000245.4 splice_region, intron

Scores

Splicing: ADA: 0.0001014

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.358

Variant links:

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]

MET links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 7-116769637-C-T is Benign according to our data. Variant chr7-116769637-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 517049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MET	NM_000245.4 link	c.2584-8C>T		splice_region_variant, intron_variant		ENST00000397752.8	NP_000236.2	P08581-1A0A024R759

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MET	ENST00000397752.8 link	c.2584-8C>T		splice_region_variant, intron_variant		1	NM_000245.4	ENSP00000380860.3		P08581-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

141

AN:

133886

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000448

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000890

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00767

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000855

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00150

AC:

2095

AN:

1396732

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

1061

AN XY:

693700

show subpopulations

Gnomad4 AFR exome

AF:

0.00629

Gnomad4 AMR exome

AF:

0.0142

Gnomad4 ASJ exome

AF:

0.00353

Gnomad4 EAS exome

AF:

0.000238

Gnomad4 SAS exome

AF:

0.00731

Gnomad4 FIN exome

AF:

0.000542

Gnomad4 NFE exome

AF:

0.000577

Gnomad4 OTH exome

AF:

0.00170

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00107

AC:

143

AN:

133956

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

64658

show subpopulations

Gnomad4 AFR

AF:

0.000502

Gnomad4 AMR

AF:

0.000888

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00767

Gnomad4 NFE

AF:

0.000855

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00106

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Renal cell carcinoma

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2025

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 30, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.089

DANN

Benign

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00010

dbscSNV1_RF

Benign

0.046

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over