chr1-41510674-T-C

Position:

• chr1-41510674-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_024503.5(HIVEP3):​c.6998A>G​(p.Glu2333Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 1,523,114 control chromosomes in the GnomAD database, including 1,227 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.029 (96 hom., cov: 33)
  • Exomes 𝑓: 0.034 (1131 hom.)
• Consequence: HIVEP3 NM_024503.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.607

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017419457).
• BP6: Variant 1-41510674-T-C is Benign according to our data. Variant chr1-41510674-T-C is described in ClinVar as [Benign]. Clinvar id is 3056543.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.094 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIVEP3	NM_024503.5	c.6998A>G	p.Glu2333Gly	missense_variant	9/9	ENST00000372583.6	NP_078779.2
HIVEP3	NM_001127714.3	c.6995A>G	p.Glu2332Gly	missense_variant	8/8		NP_001121186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIVEP3	ENST00000372583.6	c.6998A>G	p.Glu2333Gly	missense_variant	9/9	1	NM_024503.5	ENSP00000361664	P5
HIVEP3	ENST00000372584.5	c.6995A>G	p.Glu2332Gly	missense_variant	8/8	1		ENSP00000361665	A2
HIVEP3	ENST00000643665.1	c.6995A>G	p.Glu2332Gly	missense_variant	8/8			ENSP00000494598	A2
HIVEP3	ENST00000460604.1	n.1925A>G		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.0294 AC: 4470 AN: 152106 Hom.: 96 Cov.: 33

Gnomad AFR AF: 0.0195

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0379

Gnomad ASJ AF: 0.0525

Gnomad EAS AF: 0.00309

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0189

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.0306

Gnomad OTH AF: 0.0359

GnomAD3 exomes AF: 0.0417 AC: 5437 AN: 130418 Hom.: 183 AF XY: 0.0447 AC XY: 3137 AN XY: 70134

Gnomad AFR exome AF: 0.0168

Gnomad AMR exome AF: 0.0542

Gnomad ASJ exome AF: 0.0561

Gnomad EAS exome AF: 0.00243

Gnomad SAS exome AF: 0.0948

Gnomad FIN exome AF: 0.0188

Gnomad NFE exome AF: 0.0301

Gnomad OTH exome AF: 0.0429

GnomAD4 exome AF: 0.0344 AC: 47141 AN: 1370890 Hom.: 1131 Cov.: 34 AF XY: 0.0360 AC XY: 24228 AN XY: 672988

Gnomad4 AFR exome AF: 0.0205

Gnomad4 AMR exome AF: 0.0517

Gnomad4 ASJ exome AF: 0.0572

Gnomad4 EAS exome AF: 0.00375

Gnomad4 SAS exome AF: 0.0941

Gnomad4 FIN exome AF: 0.0206

Gnomad4 NFE exome AF: 0.0305

Gnomad4 OTH exome AF: 0.0399

GnomAD4 genome AF: 0.0294 AC: 4472 AN: 152224 Hom.: 96 Cov.: 33 AF XY: 0.0292 AC XY: 2176 AN XY: 74444

Gnomad4 AFR AF: 0.0196

Gnomad4 AMR AF: 0.0378

Gnomad4 ASJ AF: 0.0525

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0189

Gnomad4 NFE AF: 0.0306

Gnomad4 OTH AF: 0.0384

Alfa AF: 0.0338 Hom.: 18

Bravo AF: 0.0300

TwinsUK AF: 0.0227 AC: 84

ALSPAC AF: 0.0322 AC: 124

ESP6500AA AF: 0.0141 AC: 56

ESP6500EA AF: 0.0228 AC: 176

ExAC AF: 0.0227 AC: 2466

Asia WGS AF: 0.0700 AC: 245 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

HIVEP3-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 16, 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
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.085	.;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.57	.;T;T
MetaRNN	Benign	0.0017	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.63	.;N;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.31	.;N;N
REVEL	Benign	0.016
Sift	Benign	0.093	.;T;T
Sift4G	Benign	0.38	.;T;T
Polyphen		0.0010	B;B;B
Vest4		0.076, 0.080
MPC		0.22
ClinPred		0.00022	T
GERP RS		1.3
Varity_R		0.037
gMVP		0.092

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: rs140839222; hg19: chr1-41976345; COSMIC: COSV56024575;