rs38852

Positions:

• chr7-116714471-T-A
• chr7-116714471-T-C

Variant summary

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

The ENST00000397752.8(MET):​c.1200+14187T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,994 control chromosomes in the GnomAD database, including 13,917 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 0.41 (13917 hom., cov: 31)
• Consequence: MET ENST00000397752.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MET	NM_000245.4	c.1200+14187T>A		intron_variant		ENST00000397752.8	NP_000236.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MET	ENST00000397752.8	c.1200+14187T>A		intron_variant		1	NM_000245.4	ENSP00000380860	P3
MET	ENST00000318493.11	c.1200+14187T>A		intron_variant		1		ENSP00000317272	A2
MET	ENST00000436117.3	c.1200+14187T>A		intron_variant, NMD_transcript_variant		1		ENSP00000410980
MET	ENST00000422097.2	c.1200+14187T>A		intron_variant		3		ENSP00000398776

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61946 AN: 151876 Hom.: 13923 Cov.: 31

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.408 AC: 61963 AN: 151994 Hom.: 13917 Cov.: 31 AF XY: 0.415 AC XY: 30802 AN XY: 74302

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.430

Alfa AF: 0.433 Hom.: 1880

Bravo AF: 0.403

Asia WGS AF: 0.536 AC: 1864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.75
DANN	Benign	0.76

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: rs38852; hg19: chr7-116354525;