7-116672385-C-G

Variant names:

• chr7-116672385-C-G
• rs1858830
• ENST00000436117.3:n.-207C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000245.4(MET):​c.-207C>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
• Publications: 91 publications found

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:51196): (cytosolic oncogenic antisense to MET transcript) This gene encodes a natural antisense transcript highly expressed in papillary thyroid carcinomas harboring BRAF V600E mutation or RET gene rearrangements. This lncRNA induces the downstream MAPK pathway and is part of a co-expression network including different oncogenes belonging to the MAPK and PI3H/AKT pathways. In thyroid carcinomas, this gene has oncogenic properties associated with increased proliferation and drug resistance. [provided by RefSeq, Jan 2020]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MET	NM_000245.4	c.-207C>G		5_prime_UTR_variant	Exon 1 of 21	ENST00000397752.8	NP_000236.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MET	ENST00000397752.8	c.-207C>G		5_prime_UTR_variant	Exon 1 of 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

African (AFR) AF: 0.251 AC: 1510 AN: 6026

American (AMR) AF: 0.531 AC: 3470 AN: 6534

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 3335 AN: 7860

East Asian (EAS) AF: 0.624 AC: 12827 AN: 20560

South Asian (SAS) AF: 0.506 AC: 1445 AN: 2854

European-Finnish (FIN) AF: 0.489 AC: 9859 AN: 20168

Middle Eastern (MID) AF: 0.455 AC: 511 AN: 1124

European-Non Finnish (NFE) AF: 0.443 AC: 62723 AN: 141474

Other (OTH) AF: 0.447 AC: 6418 AN: 14360

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

African (AFR) AF: 0.250 AC: 10329 AN: 41312

American (AMR) AF: 0.520 AC: 7887 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1454 AN: 3442

East Asian (EAS) AF: 0.652 AC: 3289 AN: 5042

South Asian (SAS) AF: 0.508 AC: 2441 AN: 4806

European-Finnish (FIN) AF: 0.505 AC: 5174 AN: 10254

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.440 AC: 29573 AN: 67242

Other (OTH) AF: 0.412 AC: 862 AN: 2092

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

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 17053076, 24150225, 24909855, 23097380, 19681062) -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Renal cell carcinoma Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.1
DANN	Benign	0.85
PhyloP100		-1.1
PromoterAI		0.013	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1858830; hg19: chr7-116312439;