rs2237711

chr7-116697943-C-Achr7-116697943-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.-14-1128C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0716 in 152,230 control chromosomes in the GnomAD database, including 449 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 0.072 (449 hom., cov: 32)
• Consequence: MET NM_000245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379

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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MET	NM_000245.4	c.-14-1128C>A		intron_variant		ENST00000397752.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MET	ENST00000397752.8	c.-14-1128C>A		intron_variant		1	NM_000245.4	P3

Frequencies

GnomAD3 genomes AF: 0.0717 AC: 10906 AN: 152112 Hom.: 452 Cov.: 32

Gnomad AFR AF: 0.0413

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0505

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0783

Gnomad OTH AF: 0.0614

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

GnomAD4 genome AF: 0.0716 AC: 10895 AN: 152230 Hom.: 449 Cov.: 32 AF XY: 0.0745 AC XY: 5546 AN XY: 74420

Gnomad4 AFR AF: 0.0412

Gnomad4 AMR AF: 0.0504

Gnomad4 ASJ AF: 0.0971

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.0783

Gnomad4 OTH AF: 0.0621

Alfa AF: 0.0694 Hom.: 417

Bravo AF: 0.0639

Asia WGS AF: 0.0880 AC: 306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	1.2
Dann	Benign	0.78

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: rs2237711; hg19: chr7-116337997;