1-41510994-G-A

Position:

• chr1-41510994-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_024503.5(HIVEP3):​c.6678C>T​(p.Ser2226=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,613,526 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0067 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (16 hom.)
• Consequence: HIVEP3 NM_024503.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.69

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-41510994-G-A is Benign according to our data. Variant chr1-41510994-G-A is described in ClinVar as [Benign]. Clinvar id is 3039552.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.69 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00668 (1017/152318) while in subpopulation AFR AF= 0.0172 (716/41564). AF 95% confidence interval is 0.0162. There are 6 homozygotes in gnomad4. There are 551 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIVEP3	NM_024503.5	c.6678C>T	p.Ser2226=	synonymous_variant	9/9	ENST00000372583.6	NP_078779.2
HIVEP3	NM_001127714.3	c.6675C>T	p.Ser2225=	synonymous_variant	8/8		NP_001121186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIVEP3	ENST00000372583.6	c.6678C>T	p.Ser2226=	synonymous_variant	9/9	1	NM_024503.5	ENSP00000361664	P5
HIVEP3	ENST00000372584.5	c.6675C>T	p.Ser2225=	synonymous_variant	8/8	1		ENSP00000361665	A2
HIVEP3	ENST00000643665.1	c.6675C>T	p.Ser2225=	synonymous_variant	8/8			ENSP00000494598	A2
HIVEP3	ENST00000460604.1	n.1605C>T		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.00664 AC: 1010 AN: 152200 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.0120

Gnomad SAS AF: 0.00993

Gnomad FIN AF: 0.00809

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000970

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00437 AC: 1088 AN: 248708 Hom.: 8 AF XY: 0.00435 AC XY: 587 AN XY: 134958

Gnomad AFR exome AF: 0.0168

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00160

Gnomad EAS exome AF: 0.0133

Gnomad SAS exome AF: 0.00809

Gnomad FIN exome AF: 0.00613

Gnomad NFE exome AF: 0.00111

Gnomad OTH exome AF: 0.00362

GnomAD4 exome AF: 0.00196 AC: 2868 AN: 1461208 Hom.: 16 Cov.: 34 AF XY: 0.00211 AC XY: 1535 AN XY: 726892

Gnomad4 AFR exome AF: 0.0173

Gnomad4 AMR exome AF: 0.00121

Gnomad4 ASJ exome AF: 0.00126

Gnomad4 EAS exome AF: 0.00642

Gnomad4 SAS exome AF: 0.00840

Gnomad4 FIN exome AF: 0.00546

Gnomad4 NFE exome AF: 0.000600

Gnomad4 OTH exome AF: 0.00358

GnomAD4 genome AF: 0.00668 AC: 1017 AN: 152318 Hom.: 6 Cov.: 32 AF XY: 0.00740 AC XY: 551 AN XY: 74474

Gnomad4 AFR AF: 0.0172

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.0120

Gnomad4 SAS AF: 0.00973

Gnomad4 FIN AF: 0.00809

Gnomad4 NFE AF: 0.000956

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00234 Hom.: 0

Bravo AF: 0.00636

Asia WGS AF: 0.0150 AC: 51 AN: 3478

EpiCase AF: 0.000763

EpiControl AF: 0.000830

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 21, 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
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.099
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs137918317; hg19: chr1-41976665;