rs2038978

chr1-41629048-A-G

Variant summary

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

The NM_024503.5(HIVEP3):c.-720-101T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 844,954 control chromosomes in the GnomAD database, including 112,683 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 0.46 (16834 hom., cov: 32)
  • Exomes 𝑓: 0.52 (95849 hom.)
• Consequence: HIVEP3 NM_024503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIVEP3	NM_024503.5	c.-720-101T>C		intron_variant		ENST00000372583.6
HIVEP3	NM_001127714.3	c.-720-101T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIVEP3	ENST00000372583.6	c.-720-101T>C		intron_variant		1	NM_024503.5	P5
HIVEP3	ENST00000372584.5	c.-720-101T>C		intron_variant		1		A2
HIVEP3	ENST00000643665.1	c.-720-101T>C		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70205 AN: 151958 Hom.: 16837 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.438

GnomAD4 exome AF: 0.523 AC: 362292 AN: 692878 Hom.: 95849 AF XY: 0.522 AC XY: 174301 AN XY: 333698

Gnomad4 AFR exome AF: 0.353

Gnomad4 AMR exome AF: 0.327

Gnomad4 ASJ exome AF: 0.537

Gnomad4 EAS exome AF: 0.332

Gnomad4 SAS exome AF: 0.429

Gnomad4 FIN exome AF: 0.489

Gnomad4 NFE exome AF: 0.541

Gnomad4 OTH exome AF: 0.507

GnomAD4 genome AF: 0.462 AC: 70222 AN: 152076 Hom.: 16834 Cov.: 32 AF XY: 0.457 AC XY: 33950 AN XY: 74336

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.540

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.436

Alfa AF: 0.489 Hom.: 2292

Bravo AF: 0.449

Asia WGS AF: 0.401 AC: 1398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.080
Dann	Benign	0.51

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: rs2038978; hg19: chr1-42094719;