7-116791952-T-C

Position:

• chr7-116791952-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000245.4(MET):​c.3799-3703T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.963 in 152,368 control chromosomes in the GnomAD database, including 70,750 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.96 (70750 hom., cov: 34)
• Consequence: MET NM_000245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MET	NM_000245.4	c.3799-3703T>C		intron_variant		ENST00000397752.8	NP_000236.2
MET	NM_001127500.3	c.3853-3703T>C		intron_variant			NP_001120972.1
MET	NM_001324402.2	c.2509-3703T>C		intron_variant			NP_001311331.1
MET	XM_011516223.2	c.3856-3703T>C		intron_variant			XP_011514525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MET	ENST00000397752.8	c.3799-3703T>C		intron_variant		1	NM_000245.4	ENSP00000380860	P3
MET	ENST00000318493.11	c.3853-3703T>C		intron_variant		1		ENSP00000317272	A2
MET	ENST00000436117.3	c.*1404-3703T>C		intron_variant, NMD_transcript_variant		1		ENSP00000410980

Frequencies

GnomAD3 genomes AF: 0.963 AC: 146680 AN: 152250 Hom.: 70705 Cov.: 34

Gnomad AFR AF: 0.990

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.960

Gnomad ASJ AF: 0.971

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.958

Gnomad FIN AF: 0.927

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.950

Gnomad OTH AF: 0.969

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

GnomAD4 genome AF: 0.963 AC: 146784 AN: 152368 Hom.: 70750 Cov.: 34 AF XY: 0.963 AC XY: 71750 AN XY: 74508

Gnomad4 AFR AF: 0.990

Gnomad4 AMR AF: 0.959

Gnomad4 ASJ AF: 0.971

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.957

Gnomad4 FIN AF: 0.927

Gnomad4 NFE AF: 0.950

Gnomad4 OTH AF: 0.970

Alfa AF: 0.952 Hom.: 8612

Bravo AF: 0.967

Asia WGS AF: 0.982 AC: 3413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.23

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: rs193687; hg19: chr7-116432006;