1-41510461-G-C

Position:

• chr1-41510461-G-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.7211C>G​(p.Pro2404Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00512 in 1,501,116 control chromosomes in the GnomAD database, including 361 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 0.027 (203 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (158 hom.)
• Consequence: HIVEP3 NM_024503.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0340

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=0.0017612576).
• BP6: Variant 1-41510461-G-C is Benign according to our data. Variant chr1-41510461-G-C is described in ClinVar as [Benign]. Clinvar id is 3037152.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIVEP3	NM_024503.5	c.7211C>G	p.Pro2404Arg	missense_variant	9/9	ENST00000372583.6	NP_078779.2
HIVEP3	NM_001127714.3	c.7208C>G	p.Pro2403Arg	missense_variant	8/8		NP_001121186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIVEP3	ENST00000372583.6	c.7211C>G	p.Pro2404Arg	missense_variant	9/9	1	NM_024503.5	ENSP00000361664	P5
HIVEP3	ENST00000372584.5	c.7208C>G	p.Pro2403Arg	missense_variant	8/8	1		ENSP00000361665	A2
HIVEP3	ENST00000643665.1	c.7208C>G	p.Pro2403Arg	missense_variant	8/8			ENSP00000494598	A2
HIVEP3	ENST00000460604.1	n.2138C>G		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.0272 AC: 4139 AN: 152106 Hom.: 203 Cov.: 33

Gnomad AFR AF: 0.0944

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0234

GnomAD3 exomes AF: 0.00751 AC: 1230 AN: 163864 Hom.: 52 AF XY: 0.00576 AC XY: 505 AN XY: 87674

Gnomad AFR exome AF: 0.0942

Gnomad AMR exome AF: 0.00335

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000142

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000199

Gnomad OTH exome AF: 0.00244

GnomAD4 exome AF: 0.00262 AC: 3538 AN: 1348894 Hom.: 158 Cov.: 29 AF XY: 0.00234 AC XY: 1542 AN XY: 659864

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.00430

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000130

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000170

Gnomad4 OTH exome AF: 0.00529

GnomAD4 genome AF: 0.0272 AC: 4144 AN: 152222 Hom.: 203 Cov.: 33 AF XY: 0.0269 AC XY: 2001 AN XY: 74446

Gnomad4 AFR AF: 0.0943

Gnomad4 AMR AF: 0.0109

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000177

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.00147 Hom.: 5

Bravo AF: 0.0312

ESP6500AA AF: 0.0867 AC: 382

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00765 AC: 925

Asia WGS AF: 0.00433 AC: 15 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

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). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	14
DANN	Benign	0.74
DEOGEN2	Benign	0.13	.;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.37	.;T;T
MetaRNN	Benign	0.0018	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.90	.;L;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.2	.;N;N
REVEL	Benign	0.036
Sift	Benign	0.29	.;T;T
Sift4G	Pathogenic	0.0	.;D;D
Polyphen		0.0	B;B;B
Vest4		0.048, 0.11
MVP		0.061
MPC		0.76
ClinPred		0.0024	T
GERP RS		-1.3
Varity_R		0.034
gMVP		0.058

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: rs74071559; hg19: chr1-41976132;