1-41513485-A-G

Position:

• chr1-41513485-A-G

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.5736T>C​(p.Ala1912=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 1,608,538 control chromosomes in the GnomAD database, including 328,493 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (32343 hom., cov: 31)
  • Exomes 𝑓: 0.63 (296150 hom.)
• Consequence: HIVEP3 NM_024503.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.830

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=-0.85).
• BP6: Variant 1-41513485-A-G is Benign according to our data. Variant chr1-41513485-A-G is described in ClinVar as [Benign]. Clinvar id is 402943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.83 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIVEP3	NM_024503.5	c.5736T>C	p.Ala1912=	synonymous_variant	8/9	ENST00000372583.6
HIVEP3	NM_001127714.3	c.5736T>C	p.Ala1912=	synonymous_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIVEP3	ENST00000372583.6	c.5736T>C	p.Ala1912=	synonymous_variant	8/9	1	NM_024503.5	P5
HIVEP3	ENST00000372584.5	c.5736T>C	p.Ala1912=	synonymous_variant	7/8	1		A2
HIVEP3	ENST00000643665.1	c.5736T>C	p.Ala1912=	synonymous_variant	7/8			A2
HIVEP3	ENST00000460604.1	n.663T>C		non_coding_transcript_exon_variant	4/5	2

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98349 AN: 151752 Hom.: 32315 Cov.: 31

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.618

GnomAD3 exomes AF: 0.670 AC: 163045 AN: 243254 Hom.: 56083 AF XY: 0.665 AC XY: 88176 AN XY: 132514

Gnomad AFR exome AF: 0.656

Gnomad AMR exome AF: 0.719

Gnomad ASJ exome AF: 0.643

Gnomad EAS exome AF: 0.996

Gnomad SAS exome AF: 0.694

Gnomad FIN exome AF: 0.660

Gnomad NFE exome AF: 0.602

Gnomad OTH exome AF: 0.638

GnomAD4 exome AF: 0.633 AC: 922403 AN: 1456668 Hom.: 296150 Cov.: 76 AF XY: 0.634 AC XY: 459276 AN XY: 724360

Gnomad4 AFR exome AF: 0.650

Gnomad4 AMR exome AF: 0.711

Gnomad4 ASJ exome AF: 0.637

Gnomad4 EAS exome AF: 0.992

Gnomad4 SAS exome AF: 0.689

Gnomad4 FIN exome AF: 0.658

Gnomad4 NFE exome AF: 0.610

Gnomad4 OTH exome AF: 0.654

GnomAD4 genome AF: 0.648 AC: 98428 AN: 151870 Hom.: 32343 Cov.: 31 AF XY: 0.654 AC XY: 48493 AN XY: 74202

Gnomad4 AFR AF: 0.653

Gnomad4 AMR AF: 0.682

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.990

Gnomad4 SAS AF: 0.712

Gnomad4 FIN AF: 0.664

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.616

Alfa AF: 0.618 Hom.: 9018

Bravo AF: 0.649

Asia WGS AF: 0.806 AC: 2803 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

HIVEP3-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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	-0.85
CADD	Benign	1.7
DANN	Benign	0.37

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: rs615177; hg19: chr1-41979156; COSMIC: COSV56020321;