rs10487353

chr7-116683882-G-T

Variant summary

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

The NM_000245.4(MET):c.-15+11305G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,148 control chromosomes in the GnomAD database, including 2,166 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 0.13 (2166 hom., cov: 32)
• Consequence: MET NM_000245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.08).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MET	NM_000245.4	c.-15+11305G>T		intron_variant		ENST00000397752.8
COMETT	NR_165032.1	n.87+4059C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MET	ENST00000397752.8	c.-15+11305G>T		intron_variant		1	NM_000245.4	P3

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19449 AN: 152028 Hom.: 2147 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.0747

Gnomad AMR AF: 0.0835

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.0190

Gnomad SAS AF: 0.0730

Gnomad FIN AF: 0.0541

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0612

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.128 AC: 19506 AN: 152148 Hom.: 2166 Cov.: 32 AF XY: 0.124 AC XY: 9252 AN XY: 74398

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.0835

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.0189

Gnomad4 SAS AF: 0.0729

Gnomad4 FIN AF: 0.0541

Gnomad4 NFE AF: 0.0612

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0652 Hom.: 297

Bravo AF: 0.138

Asia WGS AF: 0.0850 AC: 295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.65
Dann	Benign	0.51

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: rs10487353; hg19: chr7-116323936;