Variant chr7-116695757-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000245.4(MET):c.-14-3314A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0477 in 490,252 control chromosomes in the GnomAD database, including 761 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.059 ( 341 hom., cov: 32)

Exomes 𝑓: 0.043 ( 420 hom. )

Consequence

MET
NM_000245.4 intron

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -0.325

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 (MetaRNN=0.0027790964).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MET	NM_000245.4 linkuse as main transcript	c.-14-3314A>T		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 linkuse as main transcript	c.-14-3314A>T		intron_variant		1	NM_000245.4	ENSP00000380860.3		P08581-1

Frequencies

GnomAD3 genomes

AF:

0.0586

AC:

8911

AN:

152164

Hom.:

335

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0959

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.0796

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.0695

Gnomad SAS

AF:

0.0447

Gnomad FIN

AF:

0.00932

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0409

Gnomad OTH

AF:

0.0511

GnomAD3 exomes

AF:

0.0475

AC:

6981

AN:

147110

Hom.:

228

AF XY:

0.0460

AC XY:

3645

AN XY:

79308

show subpopulations

Gnomad AFR exome

AF:

0.0990

Gnomad AMR exome

AF:

0.0755

Gnomad ASJ exome

AF:

0.0248

Gnomad EAS exome

AF:

0.0672

Gnomad SAS exome

AF:

0.0389

Gnomad FIN exome

AF:

0.0103

Gnomad NFE exome

AF:

0.0432

Gnomad OTH exome

AF:

0.0453

GnomAD4 exome

AF:

0.0428

AC:

14458

AN:

337970

Hom.:

420

Cov.:

AF XY:

0.0426

AC XY:

8029

AN XY:

188650

show subpopulations

Gnomad4 AFR exome

AF:

0.101

Gnomad4 AMR exome

AF:

0.0757

Gnomad4 ASJ exome

AF:

0.0244

Gnomad4 EAS exome

AF:

0.0666

Gnomad4 SAS exome

AF:

0.0393

Gnomad4 FIN exome

AF:

0.0105

Gnomad4 NFE exome

AF:

0.0396

Gnomad4 OTH exome

AF:

0.0445

GnomAD4 genome

AF:

0.0587

AC:

8944

AN:

152282

Hom.:

341

Cov.:

AF XY:

0.0581

AC XY:

4323

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0962

Gnomad4 AMR

AF:

0.0794

Gnomad4 ASJ

AF:

0.0248

Gnomad4 EAS

AF:

0.0697

Gnomad4 SAS

AF:

0.0450

Gnomad4 FIN

AF:

0.00932

Gnomad4 NFE

AF:

0.0409

Gnomad4 OTH

AF:

0.0549

Alfa

AF:

0.0461

Hom.:

Bravo

AF:

0.0647

TwinsUK

AF:

0.0472

AC:

175

ALSPAC

AF:

0.0446

AC:

172

ExAC

AF:

0.0354

AC:

687

Asia WGS

AF:

0.0710

AC:

247

AN:

3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.6

DANN

Benign

0.34

Eigen

Benign

-0.88

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.034

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0028

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

P;P

PROVEAN

Benign

0.0

REVEL

Benign

0.017

Sift

Pathogenic

0.0

MutPred

0.87

Loss of MoRF binding (P = 0.148);

ClinPred

0.0018

GERP RS

-2.0

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

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