Variant chr1-156752232-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001319186.2(HDGF):c.132T>A(p.His44Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

HDGF
NM_001319186.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.102

Variant links:

Genes affected

HDGF (HGNC:):

HDGF links:

HDGF (HGNC:4856): (heparin binding growth factor) This gene encodes a member of the hepatoma-derived growth factor family. The encoded protein has mitogenic and DNA-binding activity and may play a role in cellular proliferation and differentiation. High levels of expression of this gene enhance the growth of many tumors. This gene was thought initially to be located on chromosome X; however, that location has been determined to correspond to a related pseudogene. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jan 2016]

HDGF links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06666753).

BP6

Variant 1-156752232-A-T is Benign according to our data. Variant chr1-156752232-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2252744.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein
HDGF	NM_001319186.2 linkuse as main transcript	c.132T>A	p.His44Gln	missense_variant	1/6	NP_001306115.1
HDGF	NM_001126050.2 linkuse as main transcript	c.132T>A	p.His44Gln	missense_variant	1/6	NP_001119522.1
HDGF	NM_001126051.1 linkuse as main transcript	c.-129T>A		5_prime_UTR_variant	1/6	NP_001119523.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
HDGF	ENST00000465180.5 linkuse as main transcript	n.501+3305T>A		intron_variant		1
HDGF	ENST00000368206.5 linkuse as main transcript	c.132T>A	p.His44Gln	missense_variant	1/6	5	ENSP00000357189.5	P51858-3
HDGF	ENST00000368209.9 linkuse as main transcript	c.-129T>A		5_prime_UTR_variant	1/6	2	ENSP00000357192.5	P51858-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000648

AC:

AN:

154306

Hom.:

AF XY:

0.0000122

AC XY:

AN XY:

81966

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000171

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000214

AC:

AN:

1399420

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

690220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000185

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

ExAC

AF:

0.0000395

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 28, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.76

CADD

Benign

9.0

DANN

Benign

0.70

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0026

LIST_S2

Benign

0.20

M_CAP

Benign

0.0020

MetaRNN

Benign

0.067

MetaSVM

Benign

-0.97

PROVEAN

Benign

0.20

REVEL

Benign

0.015

Sift

Benign

0.045

Sift4G

Uncertain

0.040

Vest4

0.14

MutPred

0.43

Gain of solvent accessibility (P = 0.0155);

MVP

0.092

MPC

0.43

ClinPred

0.53

GERP RS

2.0

gMVP

0.93

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over