rs1040994

Variant names:

• chr6-12196980-C-A
• rs1040994
• ENST00000789282.1:n.116-12670G>T

Variant summary

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

The ENST00000789282.1(ENSG00000302734):​n.116-12670G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,070 control chromosomes in the GnomAD database, including 2,009 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 0.15 (2009 hom., cov: 31)
• Consequence: ENSG00000302734 ENST00000789282.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41
• Publications: 9 publications found

Genes affected

ENSG00000302734 (HGNC:):

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIVEP1	XR_007059258.1	n.7531-2241C>A		intron_variant	Intron 10 of 11
HIVEP1	XR_007059259.1	n.6799-2241C>A		intron_variant	Intron 8 of 9
HIVEP1	XR_007059260.1	n.6741-2241C>A		intron_variant	Intron 8 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000302734	ENST00000789282.1	n.116-12670G>T		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22285 AN: 151952 Hom.: 2013 Cov.: 31

Gnomad AFR AF: 0.0588

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0308

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.147 AC: 22284 AN: 152070 Hom.: 2009 Cov.: 31 AF XY: 0.144 AC XY: 10719 AN XY: 74354

African (AFR) AF: 0.0589 AC: 2442 AN: 41474

American (AMR) AF: 0.137 AC: 2086 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3470

East Asian (EAS) AF: 0.0310 AC: 161 AN: 5186

South Asian (SAS) AF: 0.179 AC: 862 AN: 4814

European-Finnish (FIN) AF: 0.129 AC: 1364 AN: 10568

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14186 AN: 67968

Other (OTH) AF: 0.173 AC: 365 AN: 2114

Alfa AF: 0.189 Hom.: 8365

Bravo AF: 0.141

Asia WGS AF: 0.0970 AC: 337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.033
DANN	Benign	0.50
PhyloP100		-2.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1040994; hg19: chr6-12197213;