chr1-41510546-G-A

Variant names:

• chr1-41510546-G-A
• rs72669005
• NM_024503.5:c.7126C>T

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.7126C>T​(p.Pro2376Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 1,576,608 control chromosomes in the GnomAD database, including 3,656 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 (★★).

• Frequency:
  • Genomes: 𝑓 0.086 (913 hom., cov: 33)
  • Exomes 𝑓: 0.053 (2743 hom.)
• Consequence: HIVEP3 NM_024503.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.17
• Publications: 10 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=0.0012972653).
• BP6: Variant 1-41510546-G-A is Benign according to our data. Variant chr1-41510546-G-A is described in ClinVar as Benign. ClinVar VariationId is 402940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 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.7126C>T	p.Pro2376Ser	missense	Exon 9 of 9	NP_078779.2
	HIVEP3	NM_001127714.3		c.7123C>T	p.Pro2375Ser	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.7126C>T	p.Pro2376Ser	missense	Exon 9 of 9	ENSP00000361664.1
	HIVEP3	ENST00000372584.5	TSL:1	c.7123C>T	p.Pro2375Ser	missense	Exon 8 of 8	ENSP00000361665.1
	HIVEP3	ENST00000643665.1		c.7123C>T	p.Pro2375Ser	missense	Exon 8 of 8	ENSP00000494598.1

Frequencies

GnomAD3 genomes AF: 0.0859 AC: 13063 AN: 152078 Hom.: 907 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0584

Gnomad ASJ AF: 0.0522

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0369

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0452

Gnomad OTH AF: 0.0766

GnomAD2 exomes AF: 0.0659 AC: 12199 AN: 185134 AF XY: 0.0671

Gnomad AFR exome AF: 0.201

Gnomad AMR exome AF: 0.0659

Gnomad ASJ exome AF: 0.0557

Gnomad EAS exome AF: 0.00310

Gnomad FIN exome AF: 0.0356

Gnomad NFE exome AF: 0.0489

Gnomad OTH exome AF: 0.0589

GnomAD4 exome AF: 0.0527 AC: 75009 AN: 1424412 Hom.: 2743 Cov.: 30 AF XY: 0.0539 AC XY: 38023 AN XY: 704980

African (AFR) AF: 0.197 AC: 6432 AN: 32662

American (AMR) AF: 0.0641 AC: 2527 AN: 39444

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 1422 AN: 25422

East Asian (EAS) AF: 0.00365 AC: 138 AN: 37818

South Asian (SAS) AF: 0.114 AC: 9266 AN: 81194

European-Finnish (FIN) AF: 0.0366 AC: 1849 AN: 50554

Middle Eastern (MID) AF: 0.118 AC: 615 AN: 5226

European-Non Finnish (NFE) AF: 0.0450 AC: 49157 AN: 1093184

Other (OTH) AF: 0.0612 AC: 3603 AN: 58908

GnomAD4 genome AF: 0.0861 AC: 13100 AN: 152196 Hom.: 913 Cov.: 33 AF XY: 0.0851 AC XY: 6332 AN XY: 74420

African (AFR) AF: 0.188 AC: 7794 AN: 41510

American (AMR) AF: 0.0582 AC: 891 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0522 AC: 181 AN: 3468

East Asian (EAS) AF: 0.00252 AC: 13 AN: 5164

South Asian (SAS) AF: 0.114 AC: 552 AN: 4824

European-Finnish (FIN) AF: 0.0369 AC: 392 AN: 10616

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0452 AC: 3076 AN: 67992

Other (OTH) AF: 0.0777 AC: 164 AN: 2112

Alfa AF: 0.0516 Hom.: 177

Bravo AF: 0.0916

TwinsUK AF: 0.0361 AC: 134

ALSPAC AF: 0.0480 AC: 185

ESP6500AA AF: 0.180 AC: 790

ESP6500EA AF: 0.0496 AC: 426

ExAC AF: 0.0574 AC: 6830

Asia WGS AF: 0.0870 AC: 304 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: MAF

HIVEP3-related disorder Benign:1

Apr 05, 2024

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	0.16
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.044
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.2
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.027
Sift	Benign	0.050	D
Sift4G	Benign	0.077	T
Polyphen		0.87	P
Vest4		0.073
MPC		0.30
ClinPred		0.012	T
GERP RS		4.3
Varity_R		0.092
gMVP		0.085
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: rs72669005; hg19: chr1-41976217; COSMIC: COSV107210339;