6-12048594-A-G

Variant names:

• chr6-12048594-A-G
• rs1570989
• NM_002114.4:c.40+32926A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002114.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIVEP1	NM_002114.4	MANE Select	c.40+32926A>G		intron	N/A	NP_002105.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIVEP1	ENST00000379388.7	TSL:1 MANE Select	c.40+32926A>G		intron	N/A	ENSP00000368698.2
	HIVEP1	ENST00000478545.2	TSL:4	c.40+32926A>G		intron	N/A	ENSP00000418021.2
	HIVEP1	ENST00000487103.6	TSL:2	c.40+32926A>G		intron	N/A	ENSP00000417348.2

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

African (AFR) AF: 0.810 AC: 33612 AN: 41480

American (AMR) AF: 0.795 AC: 12147 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2787 AN: 3470

East Asian (EAS) AF: 0.810 AC: 4197 AN: 5182

South Asian (SAS) AF: 0.811 AC: 3915 AN: 4826

European-Finnish (FIN) AF: 0.739 AC: 7808 AN: 10566

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.770 AC: 52368 AN: 68006

Other (OTH) AF: 0.790 AC: 1671 AN: 2114

Alfa AF: 0.779 Hom.: 168438

Bravo AF: 0.791

Asia WGS AF: 0.775 AC: 2694 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.52
DANN	Benign	0.34
PhyloP100		-0.42
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: rs1570989; hg19: chr6-12048827;