rs2073560

chr7-116783107-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000245.4(MET):c.3633-197G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,128 control chromosomes in the GnomAD database, including 2,007 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (2007 hom., cov: 33)
• Consequence: MET NM_000245.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.972

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-116783107-G-A is Benign according to our data. Variant chr7-116783107-G-A is described in ClinVar as [Benign]. Clinvar id is 1241630.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MET	NM_000245.4	c.3633-197G>A		intron_variant		ENST00000397752.8
MET	NM_001127500.3	c.3687-197G>A		intron_variant
MET	NM_001324402.2	c.2343-197G>A		intron_variant
MET	XM_011516223.2	c.3690-197G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MET	ENST00000397752.8	c.3633-197G>A		intron_variant		1	NM_000245.4	P3
MET	ENST00000318493.11	c.3687-197G>A		intron_variant		1		A2
MET	ENST00000436117.3	c.*1238-197G>A		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22095 AN: 152010 Hom.: 2009 Cov.: 33

Gnomad AFR AF: 0.0410

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.145 AC: 22092 AN: 152128 Hom.: 2007 Cov.: 33 AF XY: 0.147 AC XY: 10916 AN XY: 74342

Gnomad4 AFR AF: 0.0409

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.144

Alfa AF: 0.157 Hom.: 268

Bravo AF: 0.133

Asia WGS AF: 0.251 AC: 870 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.5
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: rs2073560; hg19: chr7-116423161; COSMIC: COSV104403451;