chr7-116672385-C-G

Position:

• chr7-116672385-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000245.4(MET):​c.-195C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 371,524 control chromosomes in the GnomAD database, including 37,707 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13510 hom., cov: 32)
  • Exomes 𝑓: 0.46 (24197 hom.)
• Consequence: MET NM_000245.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.05

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]

COMETT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 7-116672385-C-G is Benign according to our data. Variant chr7-116672385-C-G is described in ClinVar as [Benign]. Clinvar id is 1166750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MET	NM_000245.4	c.-195C>G		5_prime_UTR_variant	1/21	ENST00000397752.8	NP_000236.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MET	ENST00000397752	c.-195C>G		5_prime_UTR_variant	1/21	1	NM_000245.4	ENSP00000380860.3

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61456 AN: 150456 Hom.: 13506 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.412

GnomAD4 exome AF: 0.462 AC: 102098 AN: 220960 Hom.: 24197 Cov.: 0 AF XY: 0.462 AC XY: 52121 AN XY: 112870

Gnomad4 AFR exome AF: 0.251

Gnomad4 AMR exome AF: 0.531

Gnomad4 ASJ exome AF: 0.424

Gnomad4 EAS exome AF: 0.624

Gnomad4 SAS exome AF: 0.506

Gnomad4 FIN exome AF: 0.489

Gnomad4 NFE exome AF: 0.443

Gnomad4 OTH exome AF: 0.447

GnomAD4 genome AF: 0.408 AC: 61475 AN: 150564 Hom.: 13510 Cov.: 32 AF XY: 0.418 AC XY: 30704 AN XY: 73514

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.412

Alfa AF: 0.426 Hom.: 1738

Bravo AF: 0.403

Asia WGS AF: 0.563 AC: 1930 AN: 3432

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	This variant is associated with the following publications: (PMID: 17053076, 24150225, 24909855, 23097380, 19681062) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Renal cell carcinoma Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.1
DANN	Benign	0.85

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1858830; hg19: chr7-116312439;