7-116697298-T-G

Variant summary

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

The NM_000245.4(MET):c.-14-1773T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,910 control chromosomes in the GnomAD database, including 7,561 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 0.31 (7561 hom., cov: 32)
• Consequence: MET NM_000245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MET	NM_000245.4	c.-14-1773T>G		intron_variant		ENST00000397752.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MET	ENST00000397752.8	c.-14-1773T>G		intron_variant		1	NM_000245.4	P3

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47547 AN: 151792 Hom.: 7529 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.314 AC: 47628 AN: 151910 Hom.: 7561 Cov.: 32 AF XY: 0.312 AC XY: 23134 AN XY: 74232

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.307

Alfa AF: 0.302 Hom.: 3532

Bravo AF: 0.312

Asia WGS AF: 0.422 AC: 1463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.5
Dann	Benign	0.41

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: rs2237710; hg19: chr7-116337352;