1-41765435-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIVEP3	NM_024503.5	MANE Select	c.-800-64440A>G		intron	N/A	NP_078779.2	Q5T1R4-1
	HIVEP3	NM_001127714.3		c.-720-136488A>G		intron	N/A	NP_001121186.1	Q5T1R4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIVEP3	ENST00000372583.6	TSL:1 MANE Select	c.-800-64440A>G		intron	N/A	ENSP00000361664.1	Q5T1R4-1
	HIVEP3	ENST00000372584.5	TSL:1	c.-720-136488A>G		intron	N/A	ENSP00000361665.1	Q5T1R4-2

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

African (AFR) AF: 0.129 AC: 5352 AN: 41492

American (AMR) AF: 0.408 AC: 6234 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1057 AN: 3470

East Asian (EAS) AF: 0.467 AC: 2409 AN: 5158

South Asian (SAS) AF: 0.433 AC: 2088 AN: 4818

European-Finnish (FIN) AF: 0.381 AC: 4017 AN: 10552

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23444 AN: 67962

Other (OTH) AF: 0.320 AC: 676 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.83
PhyloP100		0.88
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: rs1039997; hg19: chr1-42231106;