1-41765435-T-C

Variant names:

• chr1-41765435-T-C
• rs1039997
• NM_024503.5:c.-800-64440A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024503.5(HIVEP3):​c.-800-64440A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,052 control chromosomes in the GnomAD database, including 7,912 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (7912 hom., cov: 32)
• Consequence: HIVEP3 NM_024503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.878

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIVEP3	NM_024503.5	c.-800-64440A>G		intron_variant	Intron 1 of 8	ENST00000372583.6	NP_078779.2
HIVEP3	NM_001127714.3	c.-720-136488A>G		intron_variant	Intron 1 of 7		NP_001121186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIVEP3	ENST00000372583.6	c.-800-64440A>G		intron_variant	Intron 1 of 8	1	NM_024503.5	ENSP00000361664.1
HIVEP3	ENST00000372584.5	c.-720-136488A>G		intron_variant	Intron 1 of 7	1		ENSP00000361665.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45812 AN: 151934 Hom.: 7908 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.315

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.301 AC: 45828 AN: 152052 Hom.: 7912 Cov.: 32 AF XY: 0.308 AC XY: 22902 AN XY: 74310

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.320

Alfa AF: 0.180 Hom.: 406

Bravo AF: 0.292

Asia WGS AF: 0.444 AC: 1544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.83

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: rs1039997; hg19: chr1-42231106;