rs1105414

Positions:

• chr1-41679093-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.-721+21823G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,220 control chromosomes in the GnomAD database, including 2,287 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 0.13 (2287 hom., cov: 33)
• Consequence: HIVEP3 NM_024503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.698

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 (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIVEP3	NM_024503.5	c.-721+21823G>A		intron_variant		ENST00000372583.6	NP_078779.2
HIVEP3	NM_001127714.3	c.-720-50146G>A		intron_variant			NP_001121186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIVEP3	ENST00000372583.6	c.-721+21823G>A		intron_variant		1	NM_024503.5	ENSP00000361664	P5
HIVEP3	ENST00000372584.5	c.-720-50146G>A		intron_variant		1		ENSP00000361665	A2

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19311 AN: 152102 Hom.: 2273 Cov.: 33

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0617

Gnomad ASJ AF: 0.0819

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0194

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0519

Gnomad OTH AF: 0.0934

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

GnomAD4 genome AF: 0.127 AC: 19364 AN: 152220 Hom.: 2287 Cov.: 33 AF XY: 0.126 AC XY: 9361 AN XY: 74430

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.0615

Gnomad4 ASJ AF: 0.0819

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.0199

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.0519

Gnomad4 OTH AF: 0.0924

Alfa AF: 0.0964 Hom.: 370

Bravo AF: 0.131

Asia WGS AF: 0.0290 AC: 104 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	0.17
DANN	Benign	0.32

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: rs1105414; hg19: chr1-42144764;