chr1-41510950-C-T

Position:

• chr1-41510950-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_024503.5(HIVEP3):​c.6722G>A​(p.Arg2241Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,613,586 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0022 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (12 hom.)
• Consequence: HIVEP3 NM_024503.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.459

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00291574).
• BP6: Variant 1-41510950-C-T is Benign according to our data. Variant chr1-41510950-C-T is described in ClinVar as [Benign]. Clinvar id is 3039451.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIVEP3	NM_024503.5	c.6722G>A	p.Arg2241Gln	missense_variant	9/9	ENST00000372583.6	NP_078779.2
HIVEP3	NM_001127714.3	c.6719G>A	p.Arg2240Gln	missense_variant	8/8		NP_001121186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIVEP3	ENST00000372583.6	c.6722G>A	p.Arg2241Gln	missense_variant	9/9	1	NM_024503.5	ENSP00000361664	P5
HIVEP3	ENST00000372584.5	c.6719G>A	p.Arg2240Gln	missense_variant	8/8	1		ENSP00000361665	A2
HIVEP3	ENST00000643665.1	c.6719G>A	p.Arg2240Gln	missense_variant	8/8			ENSP00000494598	A2
HIVEP3	ENST00000460604.1	n.1649G>A		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.00221 AC: 337 AN: 152188 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000844

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.0112

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00246

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00222 AC: 554 AN: 249834 Hom.: 6 AF XY: 0.00218 AC XY: 295 AN XY: 135504

Gnomad AFR exome AF: 0.000874

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.000200

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00176

Gnomad FIN exome AF: 0.0114

Gnomad NFE exome AF: 0.00195

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00146 AC: 2130 AN: 1461280 Hom.: 12 Cov.: 34 AF XY: 0.00154 AC XY: 1122 AN XY: 726944

Gnomad4 AFR exome AF: 0.000926

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00233

Gnomad4 FIN exome AF: 0.00952

Gnomad4 NFE exome AF: 0.00116

Gnomad4 OTH exome AF: 0.00144

GnomAD4 genome AF: 0.00221 AC: 337 AN: 152306 Hom.: 5 Cov.: 32 AF XY: 0.00255 AC XY: 190 AN XY: 74472

Gnomad4 AFR AF: 0.000842

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.0112

Gnomad4 NFE AF: 0.00246

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00201 Hom.: 3

Bravo AF: 0.00111

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00221 AC: 19

ExAC AF: 0.00218 AC: 265

EpiCase AF: 0.00164

EpiControl AF: 0.00119

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

May 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). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.62
CADD	Uncertain	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.093	.;T;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.78	.;T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.0029	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	.;L;.
MutationTaster	Benign	0.93	N;N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.43	.;N;N
REVEL	Benign	0.026
Sift	Pathogenic	0.0	.;D;D
Sift4G	Benign	0.12	.;T;T
Polyphen		0.012	B;B;B
Vest4		0.082, 0.096
MVP		0.20
MPC		0.22
ClinPred		0.060	T
GERP RS		3.3
Varity_R		0.12
gMVP		0.18

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: rs147749727; hg19: chr1-41976621; COSMIC: COSV56011535;