chr4-56655968-C-T

Position:

chr4-56655968-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_032495.6(HOPX):c.87G>A(p.Glu29=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0213 in 1,609,038 control chromosomes in the GnomAD database, including 809 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.020 ( 57 hom., cov: 34)

Exomes 𝑓: 0.021 ( 752 hom. )

Consequence

HOPX
NM_032495.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.13

Variant links:

Genes affected

HOPX (HGNC:24961): (HOP homeobox) The protein encoded by this gene is a homeodomain protein that lacks certain conserved residues required for DNA binding. It was reported that choriocarcinoma cell lines and tissues failed to express this gene, which suggested the possible involvement of this gene in malignant conversion of placental trophoblasts. Studies in mice suggest that this protein may interact with serum response factor (SRF) and modulate SRF-dependent cardiac-specific gene expression and cardiac development. Multiple alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Feb 2009]

HOPX links:

LOC124900708 (HGNC:):

LOC124900708 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 4-56655968-C-T is Benign according to our data. Variant chr4-56655968-C-T is described in ClinVar as [Benign]. Clinvar id is 47880.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=3.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOPX	NM_032495.6 linkuse as main transcript	c.87G>A	p.Glu29=	synonymous_variant	3/4	ENST00000420433.6
LOC124900708	XR_007058129.1 linkuse as main transcript	n.302+376C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOPX	ENST00000420433.6 linkuse as main transcript	c.87G>A	p.Glu29=	synonymous_variant	3/4	5	NM_032495.6		Q9BPY8-3

Frequencies

GnomAD3 genomes

AF:

0.0195

AC:

2970

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0132

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.0566

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.0111

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0157

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.0300

AC:

7238

AN:

241668

Hom.:

268

AF XY:

0.0332

AC XY:

4361

AN XY:

131284

show subpopulations

Gnomad AFR exome

AF:

0.0146

Gnomad AMR exome

AF:

0.0203

Gnomad ASJ exome

AF:

0.0141

Gnomad EAS exome

AF:

0.0569

Gnomad SAS exome

AF:

0.108

Gnomad FIN exome

AF:

0.0132

Gnomad NFE exome

AF:

0.0146

Gnomad OTH exome

AF:

0.0237

GnomAD4 exome

AF:

0.0214

AC:

31230

AN:

1456804

Hom.:

752

Cov.:

AF XY:

0.0238

AC XY:

17241

AN XY:

724458

show subpopulations

Gnomad4 AFR exome

AF:

0.0127

Gnomad4 AMR exome

AF:

0.0196

Gnomad4 ASJ exome

AF:

0.0139

Gnomad4 EAS exome

AF:

0.0336

Gnomad4 SAS exome

AF:

0.105

Gnomad4 FIN exome

AF:

0.0132

Gnomad4 NFE exome

AF:

0.0153

Gnomad4 OTH exome

AF:

0.0248

GnomAD4 genome

AF:

0.0195

AC:

2973

AN:

152234

Hom.:

Cov.:

AF XY:

0.0212

AC XY:

1578

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0155

Gnomad4 AMR

AF:

0.0135

Gnomad4 ASJ

AF:

0.0156

Gnomad4 EAS

AF:

0.0563

Gnomad4 SAS

AF:

0.114

Gnomad4 FIN

AF:

0.0111

Gnomad4 NFE

AF:

0.0157

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.0156

Hom.:

Bravo

AF:

0.0165

Asia WGS

AF:

0.0850

AC:

295

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Aug 24, 2017	Variant summary: The c.87G>A (p.Glu29=; also known as c.33G>A (p.E11=) in NM_139212.3) in HOPX gene is a synonymous change that involves a mildly conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in control dataset of ExAC at a frequency of 0.0365 (3551/ 97210 chrs tested, including 130 homozygotes), predominantly in individuals of South Asian descent (0.12; 1701/ 14110 chrs tested, including 111 homozygotes). These frequencies exceed the estimated maximum allele frequency for a pathogenic allele in this gene (0.000025). The variant of interest has not, to our knowledge, been reported in affected individuals via published reports, but is sited as Likely Benign by a reputable database/clinical laboratory. Taking together, the variant was classified as Benign. -
Likely benign, no assertion criteria provided	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jan 20, 2009	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.86

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

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