rs1570989

chr6-12048594-A-Gchr6-12048594-A-T

Variant summary

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

The NM_002114.4(HIVEP1):c.40+32926A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,132 control chromosomes in the GnomAD database, including 46,941 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 0.78 (46941 hom., cov: 32)
• Consequence: HIVEP1 NM_002114.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIVEP1	NM_002114.4	c.40+32926A>G		intron_variant		ENST00000379388.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIVEP1	ENST00000379388.7	c.40+32926A>G		intron_variant		1	NM_002114.4	P2

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119304 AN: 152014 Hom.: 46886 Cov.: 32

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.794

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

GnomAD4 genome AF: 0.785 AC: 119417 AN: 152132 Hom.: 46941 Cov.: 32 AF XY: 0.786 AC XY: 58435 AN XY: 74380

Gnomad4 AFR AF: 0.810

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.810

Gnomad4 SAS AF: 0.811

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.770

Gnomad4 OTH AF: 0.790

Alfa AF: 0.777 Hom.: 100917

Bravo AF: 0.791

Asia WGS AF: 0.775 AC: 2694 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.52
Dann	Benign	0.34

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: rs1570989; hg19: chr6-12048827;