rs17526983

Positions:

• chr7-116776369-G-A

Variant summary

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

The NM_000245.4(MET):​c.3260-1020G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.035 in 152,198 control chromosomes in the GnomAD database, including 120 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 0.035 (120 hom., cov: 33)
• Consequence: MET NM_000245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MET	NM_000245.4	c.3260-1020G>A		intron_variant		ENST00000397752.8
MET	NM_001127500.3	c.3314-1020G>A		intron_variant
MET	NM_001324402.2	c.1970-1020G>A		intron_variant
MET	XM_011516223.2	c.3317-1020G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MET	ENST00000397752.8	c.3260-1020G>A		intron_variant		1	NM_000245.4	P3
MET	ENST00000318493.11	c.3314-1020G>A		intron_variant		1		A2
MET	ENST00000436117.3	c.*865-1020G>A		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0350 AC: 5322 AN: 152080 Hom.: 120 Cov.: 33

Gnomad AFR AF: 0.00901

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0326

Gnomad ASJ AF: 0.0461

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00724

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0542

Gnomad OTH AF: 0.0431

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

GnomAD4 genome AF: 0.0350 AC: 5320 AN: 152198 Hom.: 120 Cov.: 33 AF XY: 0.0333 AC XY: 2477 AN XY: 74414

Gnomad4 AFR AF: 0.00896

Gnomad4 AMR AF: 0.0325

Gnomad4 ASJ AF: 0.0461

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.00725

Gnomad4 FIN AF: 0.0439

Gnomad4 NFE AF: 0.0542

Gnomad4 OTH AF: 0.0427

Alfa AF: 0.0455 Hom.: 83

Bravo AF: 0.0329

Asia WGS AF: 0.00722 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.44
DANN	Benign	0.48

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: rs17526983; hg19: chr7-116416423;