7-116672813-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000245.4(MET):c.-15+237del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0521 in 152,168 control chromosomes in the GnomAD database, including 249 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.052 (249 hom., cov: 31)
• Consequence: MET NM_000245.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.856

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 -10 ACMG points.

• BP6: Variant 7-116672813-GA-G is Benign according to our data. Variant chr7-116672813-GA-G is described in ClinVar as [Likely_benign]. Clinvar id is 676958.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MET	NM_000245.4	c.-15+237del		intron_variant		ENST00000397752.8
COMETT	NR_165032.1	n.88-8773del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MET	ENST00000397752.8	c.-15+237del		intron_variant		1	NM_000245.4	P3

Frequencies

GnomAD3 genomes AF: 0.0522 AC: 7930 AN: 152050 Hom.: 249 Cov.: 31

Gnomad AFR AF: 0.0433

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0503

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0502

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0473

Gnomad OTH AF: 0.0614

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

GnomAD4 genome AF: 0.0521 AC: 7931 AN: 152168 Hom.: 249 Cov.: 31 AF XY: 0.0543 AC XY: 4037 AN XY: 74378

Gnomad4 AFR AF: 0.0432

Gnomad4 AMR AF: 0.0501

Gnomad4 ASJ AF: 0.0674

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.0502

Gnomad4 NFE AF: 0.0473

Gnomad4 OTH AF: 0.0621

Alfa AF: 0.0150 Hom.: 2

Bravo AF: 0.0519

Asia WGS AF: 0.0890 AC: 310 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2018

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. -

Computational scores

Source: dbNSFP v4.3

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: rs141961972; hg19: chr7-116312867;