7-116769637-C-T

Variant names:

• chr7-116769637-C-T
• rs370833501
• NM_000245.4:c.2584-8C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_000245.4(MET):​c.2584-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MET NM_000245.4 splice_region, intron
• Scores: Splicing: ADA: 0.0001014
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.358

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=-0.86).
• BP6: Variant 7-116769637-C-T is Benign according to our data. Variant chr7-116769637-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 517049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MET	NM_000245.4	c.2584-8C>T		splice_region_variant, intron_variant	Intron 11 of 20	ENST00000397752.8	NP_000236.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MET	ENST00000397752.8	c.2584-8C>T		splice_region_variant, intron_variant	Intron 11 of 20	1	NM_000245.4	ENSP00000380860.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 141 AN: 133886 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.000448

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000890

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00767

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000855

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00150 AC: 2095 AN: 1396732 Hom.: 0 Cov.: 35 AF XY: 0.00153 AC XY: 1061 AN XY: 693700

Gnomad4 AFR exome AF: 0.00629

Gnomad4 AMR exome AF: 0.0142

Gnomad4 ASJ exome AF: 0.00353

Gnomad4 EAS exome AF: 0.000238

Gnomad4 SAS exome AF: 0.00731

Gnomad4 FIN exome AF: 0.000542

Gnomad4 NFE exome AF: 0.000577

Gnomad4 OTH exome AF: 0.00170

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00107 AC: 143 AN: 133956 Hom.: 0 Cov.: 31 AF XY: 0.00113 AC XY: 73 AN XY: 64658

Gnomad4 AFR AF: 0.000502

Gnomad4 AMR AF: 0.000888

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00767

Gnomad4 NFE AF: 0.000855

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00106 Hom.: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Renal cell carcinoma Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jan 30, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Papillary renal cell carcinoma type 1 Benign:1

Nov 12, 2024

Myriad Genetics, Inc.

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.089
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00010
dbscSNV1_RF	Benign	0.046
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: rs370833501; hg19: chr7-116409691;