7-116690824-C-T

Variant summary

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

The NM_000245.4(MET):c.-14-8247C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 151,990 control chromosomes in the GnomAD database, including 4,541 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 0.24 (4541 hom., cov: 32)
• Consequence: MET NM_000245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MET	NM_000245.4	c.-14-8247C>T		intron_variant		ENST00000397752.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MET	ENST00000397752.8	c.-14-8247C>T		intron_variant		1	NM_000245.4	P3

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36701 AN: 151872 Hom.: 4525 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.242 AC: 36758 AN: 151990 Hom.: 4541 Cov.: 32 AF XY: 0.241 AC XY: 17866 AN XY: 74268

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.235

Alfa AF: 0.172 Hom.: 428

Bravo AF: 0.239

Asia WGS AF: 0.317 AC: 1100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.17
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: rs2299433; hg19: chr7-116330878;