rs5745692

Variant names:

• chr7-81728950-C-G
• rs5745692
• NM_000601.6:c.1040+655G>C

Variant summary

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

The NM_000601.6(HGF):​c.1040+655G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 152,286 control chromosomes in the GnomAD database, including 64 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 0.023 (64 hom., cov: 33)
• Consequence: HGF NM_000601.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

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=-0.8).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0229 (3481/152286) while in subpopulation NFE AF= 0.0358 (2433/68016). AF 95% confidence interval is 0.0346. There are 64 homozygotes in gnomad4. There are 1659 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 64 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HGF	NM_000601.6	c.1040+655G>C		intron_variant	Intron 8 of 17	ENST00000222390.11	NP_000592.3
HGF	NM_001010932.3	c.1025+655G>C		intron_variant	Intron 8 of 17		NP_001010932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HGF	ENST00000222390.11	c.1040+655G>C		intron_variant	Intron 8 of 17	1	NM_000601.6	ENSP00000222390.5
HGF	ENST00000457544.7	c.1025+655G>C		intron_variant	Intron 8 of 17	1		ENSP00000391238.2

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3483 AN: 152168 Hom.: 63 Cov.: 33

Gnomad AFR AF: 0.00550

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.0242

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0358

Gnomad OTH AF: 0.0272

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

GnomAD4 genome AF: 0.0229 AC: 3481 AN: 152286 Hom.: 64 Cov.: 33 AF XY: 0.0223 AC XY: 1659 AN XY: 74466

Gnomad4 AFR AF: 0.00549

Gnomad4 AMR AF: 0.0242

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0116

Gnomad4 FIN AF: 0.0238

Gnomad4 NFE AF: 0.0358

Gnomad4 OTH AF: 0.0274

Alfa AF: 0.0305 Hom.: 11

Bravo AF: 0.0228

Asia WGS AF: 0.00318 AC: 11 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	5.3
DANN	Benign	0.56

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: rs5745692; hg19: chr7-81358266;