1-41513179-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_024503.5(HIVEP3):c.6042C>T(p.His2014=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00492 in 1,613,872 control chromosomes in the GnomAD database, including 353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (190 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (163 hom.)
• Consequence: HIVEP3 NM_024503.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.965

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-41513179-G-A is Benign according to our data. Variant chr1-41513179-G-A is described in ClinVar as [Benign]. Clinvar id is 775538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.965 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIVEP3	NM_024503.5	c.6042C>T	p.His2014=	synonymous_variant	8/9	ENST00000372583.6
HIVEP3	NM_001127714.3	c.6042C>T	p.His2014=	synonymous_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIVEP3	ENST00000372583.6	c.6042C>T	p.His2014=	synonymous_variant	8/9	1	NM_024503.5	P5
HIVEP3	ENST00000372584.5	c.6042C>T	p.His2014=	synonymous_variant	7/8	1		A2
HIVEP3	ENST00000643665.1	c.6042C>T	p.His2014=	synonymous_variant	7/8			A2
HIVEP3	ENST00000460604.1	n.969C>T		non_coding_transcript_exon_variant	4/5	2

Frequencies

GnomAD3 genomes AF: 0.0265 AC: 4031 AN: 152236 Hom.: 190 Cov.: 32

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00798

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0215

GnomAD3 exomes AF: 0.00653 AC: 1631 AN: 249752 Hom.: 50 AF XY: 0.00502 AC XY: 680 AN XY: 135464

Gnomad AFR exome AF: 0.0947

Gnomad AMR exome AF: 0.00310

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000204

Gnomad OTH exome AF: 0.00214

GnomAD4 exome AF: 0.00267 AC: 3898 AN: 1461518 Hom.: 163 Cov.: 84 AF XY: 0.00228 AC XY: 1661 AN XY: 727060

Gnomad4 AFR exome AF: 0.0984

Gnomad4 AMR exome AF: 0.00347

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000102

Gnomad4 OTH exome AF: 0.00505

GnomAD4 genome AF: 0.0265 AC: 4036 AN: 152354 Hom.: 190 Cov.: 32 AF XY: 0.0261 AC XY: 1945 AN XY: 74510

Gnomad4 AFR AF: 0.0927

Gnomad4 AMR AF: 0.00797

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0132 Hom.: 38

Bravo AF: 0.0301

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

HIVEP3-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 23, 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). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 02, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.37
Dann	Benign	0.28

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: rs74071561; hg19: chr1-41978850;