chr1-41510657-T-C

Variant names:

• chr1-41510657-T-C
• rs9439043
• NM_024503.5:c.7015A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024503.5(HIVEP3):​c.7015A>G​(p.Thr2339Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 1,533,770 control chromosomes in the GnomAD database, including 757,851 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.97 (71866 hom., cov: 32)
  • Exomes 𝑓: 1.0 (685985 hom.)
• Consequence: HIVEP3 NM_024503.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.588
• Publications: 19 publications found

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]

ENSG00000295052 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.3137944E-6).
• BP6: Variant 1-41510657-T-C is Benign according to our data. Variant chr1-41510657-T-C is described in ClinVar as Benign. ClinVar VariationId is 402941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024503.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIVEP3	NM_024503.5	MANE Select	c.7015A>G	p.Thr2339Ala	missense	Exon 9 of 9	NP_078779.2
	HIVEP3	NM_001127714.3		c.7012A>G	p.Thr2338Ala	missense	Exon 8 of 8	NP_001121186.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIVEP3	ENST00000372583.6	TSL:1 MANE Select	c.7015A>G	p.Thr2339Ala	missense	Exon 9 of 9	ENSP00000361664.1
	HIVEP3	ENST00000372584.5	TSL:1	c.7012A>G	p.Thr2338Ala	missense	Exon 8 of 8	ENSP00000361665.1
	HIVEP3	ENST00000643665.1		c.7012A>G	p.Thr2338Ala	missense	Exon 8 of 8	ENSP00000494598.1

Frequencies

GnomAD3 genomes AF: 0.971 AC: 147672 AN: 152118 Hom.: 71818 Cov.: 32

Gnomad AFR AF: 0.901

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.988

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.978

GnomAD2 exomes AF: 0.993 AC: 139881 AN: 140928 AF XY: 0.994

Gnomad AFR exome AF: 0.890

Gnomad AMR exome AF: 0.994

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.993

GnomAD4 exome AF: 0.996 AC: 1376544 AN: 1381534 Hom.: 685985 Cov.: 72 AF XY: 0.997 AC XY: 677562 AN XY: 679732

African (AFR) AF: 0.892 AC: 27965 AN: 31354

American (AMR) AF: 0.993 AC: 34802 AN: 35040

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 24507 AN: 24510

East Asian (EAS) AF: 1.00 AC: 35566 AN: 35566

South Asian (SAS) AF: 1.00 AC: 78167 AN: 78180

European-Finnish (FIN) AF: 1.00 AC: 43817 AN: 43820

Middle Eastern (MID) AF: 0.987 AC: 4589 AN: 4650

European-Non Finnish (NFE) AF: 0.999 AC: 1070471 AN: 1071254

Other (OTH) AF: 0.991 AC: 56660 AN: 57160

GnomAD4 genome AF: 0.971 AC: 147778 AN: 152236 Hom.: 71866 Cov.: 32 AF XY: 0.972 AC XY: 72340 AN XY: 74430

African (AFR) AF: 0.901 AC: 37404 AN: 41528

American (AMR) AF: 0.988 AC: 15120 AN: 15302

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3469 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5158 AN: 5158

South Asian (SAS) AF: 0.999 AC: 4813 AN: 4816

European-Finnish (FIN) AF: 1.00 AC: 10626 AN: 10626

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67919 AN: 68018

Other (OTH) AF: 0.978 AC: 2066 AN: 2112

Alfa AF: 0.987 Hom.: 13008

Bravo AF: 0.967

TwinsUK AF: 0.999 AC: 3705

ALSPAC AF: 0.999 AC: 3849

ESP6500AA AF: 0.915 AC: 3684

ESP6500EA AF: 0.997 AC: 7782

ExAC AF: 0.981 AC: 87682

Asia WGS AF: 0.991 AC: 3446 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Apr 30, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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).

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.22
DANN	Benign	0.13
DEOGEN2	Benign	0.053	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.0000013	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.63	N
PhyloP100		0.59
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.042
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.022
MPC		0.18
ClinPred		0.00068	T
GERP RS		2.2
Varity_R		0.027
gMVP		0.043
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9439043; hg19: chr1-41976328; COSMIC: COSV56011601;