rs2327514

Variant names:

• chr6-12117322-G-A
• rs2327514
• NM_002114.4:c.95-2568G>A

Variant summary

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

The NM_002114.4(HIVEP1):​c.95-2568G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0768 in 152,242 control chromosomes in the GnomAD database, including 646 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 0.077 (646 hom., cov: 32)
• Consequence: HIVEP1 NM_002114.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.690
• Publications: 4 publications found

Genes affected

HIVEP1 (HGNC:4920): (HIVEP zinc finger 1) This gene encodes a transcription factor belonging to the ZAS family, members of which are large proteins that contain a ZAS domain - a modular protein structure consisting of a pair of C2H2 zinc fingers with an acidic-rich region and a serine/threonine-rich sequence. These proteins bind specifically to the DNA sequence motif, GGGACTTTCC, found in the enhancer elements of several viral promoters, including human immunodeficiency virus (HIV), and to related sequences found in the enhancer elements of a number of cellular promoters. This protein binds to this sequence motif, suggesting a role in the transcriptional regulation of both viral and cellular genes. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIVEP1	NM_002114.4	c.95-2568G>A		intron_variant	Intron 3 of 8	ENST00000379388.7	NP_002105.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIVEP1	ENST00000379388.7	c.95-2568G>A		intron_variant	Intron 3 of 8	1	NM_002114.4	ENSP00000368698.2

Frequencies

GnomAD3 genomes AF: 0.0769 AC: 11696 AN: 152124 Hom.: 646 Cov.: 32

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0719

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0403

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.0937

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

GnomAD4 genome AF: 0.0768 AC: 11693 AN: 152242 Hom.: 646 Cov.: 32 AF XY: 0.0723 AC XY: 5381 AN XY: 74432

African (AFR) AF: 0.0201 AC: 834 AN: 41564

American (AMR) AF: 0.0718 AC: 1098 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 671 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5192

South Asian (SAS) AF: 0.0409 AC: 197 AN: 4814

European-Finnish (FIN) AF: 0.0649 AC: 688 AN: 10598

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7903 AN: 68002

Other (OTH) AF: 0.0927 AC: 195 AN: 2104

Alfa AF: 0.107 Hom.: 1190

Bravo AF: 0.0776

Asia WGS AF: 0.0200 AC: 70 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.60
PhyloP100		-0.69
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: rs2327514; hg19: chr6-12117555;