chr7-81733271-A-T

Position:

• chr7-81733271-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000601.6(HGF):​c.866-3492T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0205 in 151,702 control chromosomes in the GnomAD database, including 41 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 0.021 (41 hom., cov: 32)
• Consequence: HGF NM_000601.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100

Genes affected

HGF (HGNC:4893): (hepatocyte growth factor) This gene encodes a protein that binds to the hepatocyte growth factor receptor to regulate cell growth, cell motility and morphogenesis in numerous cell and tissue types. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate alpha and beta chains, which form the mature heterodimer. This protein is secreted by mesenchymal cells and acts as a multi-functional cytokine on cells of mainly epithelial origin. This protein also plays a role in angiogenesis, tumorogenesis, and tissue regeneration. Although the encoded protein is a member of the peptidase S1 family of serine proteases, it lacks peptidase activity. Mutations in this gene are associated with nonsyndromic hearing loss. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0205 (3112/151702) while in subpopulation NFE AF= 0.0299 (2025/67824). AF 95% confidence interval is 0.0288. There are 41 homozygotes in gnomad4. There are 1463 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HGF	NM_000601.6	c.866-3492T>A		intron_variant		ENST00000222390.11
HGF	NM_001010932.3	c.851-3492T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HGF	ENST00000222390.11	c.866-3492T>A		intron_variant		1	NM_000601.6	P4
HGF	ENST00000457544.7	c.851-3492T>A		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.0205 AC: 3113 AN: 151590 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.00513

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0175

Gnomad ASJ AF: 0.0403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00994

Gnomad FIN AF: 0.0301

Gnomad MID AF: 0.0163

Gnomad NFE AF: 0.0299

Gnomad OTH AF: 0.0196

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

GnomAD4 genome AF: 0.0205 AC: 3112 AN: 151702 Hom.: 41 Cov.: 32 AF XY: 0.0197 AC XY: 1463 AN XY: 74112

Gnomad4 AFR AF: 0.00511

Gnomad4 AMR AF: 0.0175

Gnomad4 ASJ AF: 0.0403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00995

Gnomad4 FIN AF: 0.0301

Gnomad4 NFE AF: 0.0299

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0159 Hom.: 2004

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.57

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: rs757832; hg19: chr7-81362587;