chr1-41510659-G-A

Position:

• chr1-41510659-G-A

Variant summary

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

The NM_024503.5(HIVEP3):​c.7013C>T​(p.Pro2338Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00504 in 1,526,972 control chromosomes in the GnomAD database, including 330 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). Synonymous variant affecting the same amino acid position (i.e. P2338P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.026 (183 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (147 hom.)
• Consequence: HIVEP3 NM_024503.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.188

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=0.0024409592).
• BP6: Variant 1-41510659-G-A is Benign according to our data. Variant chr1-41510659-G-A is described in ClinVar as [Benign]. Clinvar id is 3037301.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIVEP3	NM_024503.5	c.7013C>T	p.Pro2338Leu	missense_variant	9/9	ENST00000372583.6
HIVEP3	NM_001127714.3	c.7010C>T	p.Pro2337Leu	missense_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIVEP3	ENST00000372583.6	c.7013C>T	p.Pro2338Leu	missense_variant	9/9	1	NM_024503.5	P5
HIVEP3	ENST00000372584.5	c.7010C>T	p.Pro2337Leu	missense_variant	8/8	1		A2
HIVEP3	ENST00000643665.1	c.7010C>T	p.Pro2337Leu	missense_variant	8/8			A2
HIVEP3	ENST00000460604.1	n.1940C>T		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 3956 AN: 152162 Hom.: 183 Cov.: 33

Gnomad AFR AF: 0.0904

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00929

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0234

GnomAD3 exomes AF: 0.00618 AC: 834 AN: 135002 Hom.: 28 AF XY: 0.00505 AC XY: 366 AN XY: 72510

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.00290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000366

Gnomad SAS exome AF: 0.000623

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000318

Gnomad OTH exome AF: 0.00205

GnomAD4 exome AF: 0.00272 AC: 3737 AN: 1374692 Hom.: 147 Cov.: 34 AF XY: 0.00238 AC XY: 1608 AN XY: 675394

Gnomad4 AFR exome AF: 0.0958

Gnomad4 AMR exome AF: 0.00384

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000197

Gnomad4 SAS exome AF: 0.000710

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000223

Gnomad4 OTH exome AF: 0.00543

GnomAD4 genome AF: 0.0260 AC: 3961 AN: 152280 Hom.: 183 Cov.: 33 AF XY: 0.0257 AC XY: 1914 AN XY: 74470

Gnomad4 AFR AF: 0.0902

Gnomad4 AMR AF: 0.00928

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.00274 Hom.: 4

Bravo AF: 0.0300

ESP6500AA AF: 0.0679 AC: 273

ESP6500EA AF: 0.000644 AC: 5

ExAC AF: 0.00638 AC: 664

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

HIVEP3-related disorder Benign:1

Benign, criteria provided, single submitter

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	0.057
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.020
DANN	Benign	0.42
DEOGEN2	Benign	0.077	.;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0046	N
LIST_S2	Benign	0.57	.;T;T
MetaRNN	Benign	0.0024	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.46	.;N;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.79	.;N;N
REVEL	Benign	0.032
Sift	Benign	1.0	.;T;T
Sift4G	Benign	0.42	.;T;T
Polyphen		0.0	B;B;B
Vest4		0.032, 0.043
MVP		0.055
MPC		0.19
ClinPred		0.0014	T
GERP RS		-5.5
Varity_R		0.025
gMVP		0.028

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: rs58930436; hg19: chr1-41976330;