chr1-41536492-G-A

Variant names:

• chr1-41536492-G-A
• rs648178
• NM_024503.5:c.5208-11582C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024503.5(HIVEP3):​c.5208-11582C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,028 control chromosomes in the GnomAD database, including 5,184 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 0.25 (5184 hom., cov: 31)
• Consequence: HIVEP3 NM_024503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIVEP3	NM_024503.5	c.5208-11582C>T		intron_variant	Intron 5 of 8	ENST00000372583.6	NP_078779.2
HIVEP3	NM_001127714.3	c.5208-11582C>T		intron_variant	Intron 4 of 7		NP_001121186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIVEP3	ENST00000372583.6	c.5208-11582C>T		intron_variant	Intron 5 of 8	1	NM_024503.5	ENSP00000361664.1
HIVEP3	ENST00000372584.5	c.5208-11582C>T		intron_variant	Intron 4 of 7	1		ENSP00000361665.1
HIVEP3	ENST00000643665.1	c.5208-11582C>T		intron_variant	Intron 4 of 7			ENSP00000494598.1
HIVEP3	ENST00000460604.1	n.311-18004C>T		intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38693 AN: 151910 Hom.: 5180 Cov.: 31

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.255 AC: 38712 AN: 152028 Hom.: 5184 Cov.: 31 AF XY: 0.257 AC XY: 19112 AN XY: 74298

African (AFR) AF: 0.283 AC: 11733 AN: 41432

American (AMR) AF: 0.208 AC: 3180 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1097 AN: 3468

East Asian (EAS) AF: 0.459 AC: 2373 AN: 5168

South Asian (SAS) AF: 0.291 AC: 1399 AN: 4812

European-Finnish (FIN) AF: 0.282 AC: 2982 AN: 10558

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15021 AN: 67984

Other (OTH) AF: 0.238 AC: 504 AN: 2114

Alfa AF: 0.236 Hom.: 2167

Bravo AF: 0.252

Asia WGS AF: 0.322 AC: 1116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.1
DANN	Benign	0.85
PhyloP100		0.24
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: rs648178; hg19: chr1-42002163;