1-41510994-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_024503.5(HIVEP3):c.6678C>T(p.Ser2226=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,613,526 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0067 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 16 hom. )

Consequence

HIVEP3
NM_024503.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.69

Variant links:

Genes affected

HIVEP3 (HGNC:13561): (HIVEP zinc finger 3) This gene encodes a member of the human immunodeficiency virus type 1 enhancer-binding protein family. Members of this protein family contain multiple zinc finger and acid-rich (ZAS) domains and serine-threonine rich regions. This protein acts as a transcription factor and is able to regulate nuclear factor kappaB-mediated transcription by binding the kappaB motif in target genes. This protein also binds the recombination signal sequence that flanks the V, D, and J regions of immunoglobulin and T-cell receptors. Alternate splicing results in both coding and non-coding transcript variants. [provided by RefSeq, Sep 2011]

HIVEP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 1-41510994-G-A is Benign according to our data. Variant chr1-41510994-G-A is described in ClinVar as [Benign]. Clinvar id is 3039552.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.69 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00668 (1017/152318) while in subpopulation AFR AF= 0.0172 (716/41564). AF 95% confidence interval is 0.0162. There are 6 homozygotes in gnomad4. There are 551 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIVEP3	NM_024503.5 linkuse as main transcript	c.6678C>T	p.Ser2226=	synonymous_variant	9/9	ENST00000372583.6
HIVEP3	NM_001127714.3 linkuse as main transcript	c.6675C>T	p.Ser2225=	synonymous_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIVEP3	ENST00000372583.6 linkuse as main transcript	c.6678C>T	p.Ser2226=	synonymous_variant	9/9	1	NM_024503.5	P5	Q5T1R4-1
HIVEP3	ENST00000372584.5 linkuse as main transcript	c.6675C>T	p.Ser2225=	synonymous_variant	8/8	1		A2	Q5T1R4-2
HIVEP3	ENST00000643665.1 linkuse as main transcript	c.6675C>T	p.Ser2225=	synonymous_variant	8/8			A2	Q5T1R4-2
HIVEP3	ENST00000460604.1 linkuse as main transcript	n.1605C>T		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.00664

AC:

1010

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0120

Gnomad SAS

AF:

0.00993

Gnomad FIN

AF:

0.00809

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000970

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00437

AC:

1088

AN:

248708

Hom.:

AF XY:

0.00435

AC XY:

587

AN XY:

134958

show subpopulations

Gnomad AFR exome

AF:

0.0168

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00160

Gnomad EAS exome

AF:

0.0133

Gnomad SAS exome

AF:

0.00809

Gnomad FIN exome

AF:

0.00613

Gnomad NFE exome

AF:

0.00111

Gnomad OTH exome

AF:

0.00362

GnomAD4 exome

AF:

0.00196

AC:

2868

AN:

1461208

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

1535

AN XY:

726892

show subpopulations

Gnomad4 AFR exome

AF:

0.0173

Gnomad4 AMR exome

AF:

0.00121

Gnomad4 ASJ exome

AF:

0.00126

Gnomad4 EAS exome

AF:

0.00642

Gnomad4 SAS exome

AF:

0.00840

Gnomad4 FIN exome

AF:

0.00546

Gnomad4 NFE exome

AF:

0.000600

Gnomad4 OTH exome

AF:

0.00358

GnomAD4 genome

AF:

0.00668

AC:

1017

AN:

152318

Hom.:

Cov.:

AF XY:

0.00740

AC XY:

551

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0172

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.0120

Gnomad4 SAS

AF:

0.00973

Gnomad4 FIN

AF:

0.00809

Gnomad4 NFE

AF:

0.000956

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00234

Hom.:

Bravo

AF:

0.00636

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

HIVEP3-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

Cadd

Benign

0.099

Dann

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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