1-41510826-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_024503.5(HIVEP3):c.6846C>T(p.Gly2282=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000665 in 1,612,820 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00094 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00064 (8 hom.)
• Consequence: HIVEP3 NM_024503.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.137

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-41510826-G-A is Benign according to our data. Variant chr1-41510826-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3053174.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.137 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIVEP3	NM_024503.5	c.6846C>T	p.Gly2282=	synonymous_variant	9/9	ENST00000372583.6
HIVEP3	NM_001127714.3	c.6843C>T	p.Gly2281=	synonymous_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIVEP3	ENST00000372583.6	c.6846C>T	p.Gly2282=	synonymous_variant	9/9	1	NM_024503.5	P5
HIVEP3	ENST00000372584.5	c.6843C>T	p.Gly2281=	synonymous_variant	8/8	1		A2
HIVEP3	ENST00000643665.1	c.6843C>T	p.Gly2281=	synonymous_variant	8/8			A2
HIVEP3	ENST00000460604.1	n.1773C>T		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.000940 AC: 143 AN: 152180 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00963

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00294 AC: 727 AN: 246970 Hom.: 5 AF XY: 0.00230 AC XY: 310 AN XY: 134512

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0113

Gnomad SAS exome AF: 0.000262

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000722

Gnomad OTH exome AF: 0.000828

GnomAD4 exome AF: 0.000636 AC: 929 AN: 1460522 Hom.: 8 Cov.: 34 AF XY: 0.000553 AC XY: 402 AN XY: 726528

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0130

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00537

Gnomad4 SAS exome AF: 0.000313

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000711

Gnomad4 OTH exome AF: 0.000365

GnomAD4 genome AF: 0.000939 AC: 143 AN: 152298 Hom.: 3 Cov.: 33 AF XY: 0.00118 AC XY: 88 AN XY: 74480

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.00529

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00946

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000477 Hom.: 0

Bravo AF: 0.00178

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

HIVEP3-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 23, 2019

This variant is classified as likely 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	-0.84
Cadd	Benign	1.3
Dann	Benign	0.47

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: rs142695572; hg19: chr1-41976497;