7-116741050-A-G

Variant names:

• chr7-116741050-A-G
• rs73469198
• NM_000245.4:c.1701+25A>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.1701+25A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00533 in 1,606,758 control chromosomes in the GnomAD database, including 383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (211 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (172 hom.)
• Consequence: MET NM_000245.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-116741050-A-G is Benign according to our data. Variant chr7-116741050-A-G is described in ClinVar as [Benign]. Clinvar id is 135556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MET	NM_000245.4	c.1701+25A>G		intron_variant	Intron 5 of 20	ENST00000397752.8	NP_000236.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MET	ENST00000397752.8	c.1701+25A>G		intron_variant	Intron 5 of 20	1	NM_000245.4	ENSP00000380860.3

Frequencies

GnomAD3 genomes AF: 0.0287 AC: 4300 AN: 150084 Hom.: 210 Cov.: 32

Gnomad AFR AF: 0.0989

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0131

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000419

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00974

Gnomad NFE AF: 0.000339

Gnomad OTH AF: 0.0208

GnomAD3 exomes AF: 0.00728 AC: 1774 AN: 243726 Hom.: 88 AF XY: 0.00534 AC XY: 705 AN XY: 131916

Gnomad AFR exome AF: 0.100

Gnomad AMR exome AF: 0.00436

Gnomad ASJ exome AF: 0.000807

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000211

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000396

Gnomad OTH exome AF: 0.00355

GnomAD4 exome AF: 0.00293 AC: 4261 AN: 1456632 Hom.: 172 Cov.: 33 AF XY: 0.00252 AC XY: 1822 AN XY: 724332

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.00496

Gnomad4 ASJ exome AF: 0.000730

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000213

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000223

Gnomad4 OTH exome AF: 0.00669

GnomAD4 genome AF: 0.0287 AC: 4307 AN: 150126 Hom.: 211 Cov.: 32 AF XY: 0.0279 AC XY: 2045 AN XY: 73168

Gnomad4 AFR AF: 0.0989

Gnomad4 AMR AF: 0.0131

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000631

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000339

Gnomad4 OTH AF: 0.0207

Alfa AF: 0.0179 Hom.: 16

Bravo AF: 0.0331

Asia WGS AF: 0.00808 AC: 29 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1 Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

- -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

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	-0.85
CADD	Benign	0.33
DANN	Benign	0.36

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: rs73469198; hg19: chr7-116381104; COSMIC: COSV59258628;