rs6951311

Positions:

• chr7-116794284-G-A

Variant summary

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

The ENST00000397752.8(MET):​c.3799-1371G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 152,068 control chromosomes in the GnomAD database, including 11,164 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 0.35 (11164 hom., cov: 32)
• Consequence: MET ENST00000397752.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MET	NM_000245.4	c.3799-1371G>A		intron_variant		ENST00000397752.8	NP_000236.2
MET	NM_001127500.3	c.3853-1371G>A		intron_variant			NP_001120972.1
MET	NM_001324402.2	c.2509-1371G>A		intron_variant			NP_001311331.1
MET	XM_011516223.2	c.3856-1371G>A		intron_variant			XP_011514525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MET	ENST00000397752.8	c.3799-1371G>A		intron_variant		1	NM_000245.4	ENSP00000380860	P3
MET	ENST00000318493.11	c.3853-1371G>A		intron_variant		1		ENSP00000317272	A2
MET	ENST00000436117.3	c.*1404-1371G>A		intron_variant, NMD_transcript_variant		1		ENSP00000410980

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53303 AN: 151950 Hom.: 11177 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.350 AC: 53276 AN: 152068 Hom.: 11164 Cov.: 32 AF XY: 0.353 AC XY: 26227 AN XY: 74346

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.386

Alfa AF: 0.391 Hom.: 1598

Bravo AF: 0.346

Asia WGS AF: 0.415 AC: 1444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.74

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: rs6951311; hg19: chr7-116434338;