rs5745720

Variant names:

• chr7-81717609-G-A
• rs5745720
• NM_000601.6:c.1272-244C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-81717609-G-A
• chr7-81717609-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000601.6(HGF):​c.1272-244C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 151,932 control chromosomes in the GnomAD database, including 54,055 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.84 (54055 hom., cov: 29)
• Consequence: HGF NM_000601.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.469
• Publications: 5 publications found

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]

HGF Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 39

  Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000300407 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 7-81717609-G-A is Benign according to our data. Variant chr7-81717609-G-A is described in ClinVar as [Benign]. Clinvar id is 1286880.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HGF	NM_000601.6	c.1272-244C>T		intron_variant	Intron 10 of 17	ENST00000222390.11	NP_000592.3
HGF	NM_001010932.3	c.1257-244C>T		intron_variant	Intron 10 of 17		NP_001010932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HGF	ENST00000222390.11	c.1272-244C>T		intron_variant	Intron 10 of 17	1	NM_000601.6	ENSP00000222390.5

Frequencies

GnomAD3 genomes AF: 0.842 AC: 127759 AN: 151814 Hom.: 54007 Cov.: 29

Gnomad AFR AF: 0.918

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.914

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.843

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

GnomAD4 genome AF: 0.842 AC: 127866 AN: 151932 Hom.: 54055 Cov.: 29 AF XY: 0.841 AC XY: 62445 AN XY: 74224

African (AFR) AF: 0.917 AC: 38043 AN: 41464

American (AMR) AF: 0.867 AC: 13219 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 2999 AN: 3472

East Asian (EAS) AF: 0.858 AC: 4409 AN: 5140

South Asian (SAS) AF: 0.872 AC: 4198 AN: 4814

European-Finnish (FIN) AF: 0.780 AC: 8209 AN: 10530

Middle Eastern (MID) AF: 0.911 AC: 266 AN: 292

European-Non Finnish (NFE) AF: 0.796 AC: 54087 AN: 67956

Other (OTH) AF: 0.841 AC: 1768 AN: 2102

Alfa AF: 0.815 Hom.: 64316

Bravo AF: 0.850

Asia WGS AF: 0.857 AC: 2980 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.36
DANN	Benign	0.46
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5745720; hg19: chr7-81346925;