rs1007221

Positions:

• chr1-41574100-C-T

Variant summary

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

The NM_024503.5(HIVEP3):​c.5207+1444G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,010 control chromosomes in the GnomAD database, including 3,777 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 0.20 (3777 hom., cov: 31)
• Consequence: HIVEP3 NM_024503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIVEP3	NM_024503.5	c.5207+1444G>A		intron_variant		ENST00000372583.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIVEP3	ENST00000372583.6	c.5207+1444G>A		intron_variant		1	NM_024503.5	P5
HIVEP3	ENST00000372584.5	c.5207+1444G>A		intron_variant		1		A2
HIVEP3	ENST00000643665.1	c.5207+1444G>A		intron_variant				A2
HIVEP3	ENST00000460604.1	n.310+1444G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30077 AN: 151892 Hom.: 3772 Cov.: 31

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.198 AC: 30109 AN: 152010 Hom.: 3777 Cov.: 31 AF XY: 0.204 AC XY: 15131 AN XY: 74298

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.213

Alfa AF: 0.167 Hom.: 919

Bravo AF: 0.214

Asia WGS AF: 0.311 AC: 1085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.37

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: rs1007221; hg19: chr1-42039771;