rs17138943

Positions:

• chr7-116702226-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000245.4(MET):​c.1200+1942G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0617 in 152,106 control chromosomes in the GnomAD database, including 383 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 0.062 (383 hom., cov: 32)
• Consequence: MET NM_000245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.860

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MET	NM_000245.4	c.1200+1942G>A		intron_variant		ENST00000397752.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MET	ENST00000397752.8	c.1200+1942G>A		intron_variant		1	NM_000245.4	P3
MET	ENST00000318493.11	c.1200+1942G>A		intron_variant		1		A2
MET	ENST00000436117.3	c.1200+1942G>A		intron_variant, NMD_transcript_variant		1
MET	ENST00000422097.2	c.1200+1942G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0615 AC: 9348 AN: 151988 Hom.: 376 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0808

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.0699

Gnomad SAS AF: 0.0442

Gnomad FIN AF: 0.00944

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0416

Gnomad OTH AF: 0.0526

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

GnomAD4 genome AF: 0.0617 AC: 9386 AN: 152106 Hom.: 383 Cov.: 32 AF XY: 0.0607 AC XY: 4513 AN XY: 74360

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0806

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.0701

Gnomad4 SAS AF: 0.0444

Gnomad4 FIN AF: 0.00944

Gnomad4 NFE AF: 0.0416

Gnomad4 OTH AF: 0.0563

Alfa AF: 0.0506 Hom.: 226

Bravo AF: 0.0679

Asia WGS AF: 0.0740 AC: 259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.81

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: rs17138943; hg19: chr7-116342280;