chr1-41629048-A-G

Variant names:

• chr1-41629048-A-G
• rs2038978
• NM_024503.5:c.-720-101T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ENSG00000284895 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HIVEP3	NM_024503.5	c.-720-101T>C		intron_variant	Intron 2 of 8	ENST00000372583.6	NP_078779.2
HIVEP3	NM_001127714.3	c.-720-101T>C		intron_variant	Intron 1 of 7		NP_001121186.1
LOC128125817	NM_001415000.1	c.-232T>C		upstream_gene_variant			NP_001401929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIVEP3	ENST00000372583.6	c.-720-101T>C		intron_variant	Intron 2 of 8	1	NM_024503.5	ENSP00000361664.1
HIVEP3	ENST00000372584.5	c.-720-101T>C		intron_variant	Intron 1 of 7	1		ENSP00000361665.1
HIVEP3	ENST00000643665.1	c.-720-101T>C		intron_variant	Intron 1 of 7			ENSP00000494598.1
ENSG00000284895	ENST00000646142.1	c.-232T>C		upstream_gene_variant				ENSP00000494286.1

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

African (AFR) AF: 0.353 AC: 5332 AN: 15110

American (AMR) AF: 0.327 AC: 2278 AN: 6972

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 6136 AN: 11428

East Asian (EAS) AF: 0.332 AC: 7508 AN: 22622

South Asian (SAS) AF: 0.429 AC: 4837 AN: 11280

European-Finnish (FIN) AF: 0.489 AC: 8822 AN: 18038

Middle Eastern (MID) AF: 0.473 AC: 980 AN: 2074

European-Non Finnish (NFE) AF: 0.541 AC: 311127 AN: 575238

Other (OTH) AF: 0.507 AC: 15272 AN: 30116

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

African (AFR) AF: 0.363 AC: 15056 AN: 41468

American (AMR) AF: 0.373 AC: 5704 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1872 AN: 3468

East Asian (EAS) AF: 0.408 AC: 2114 AN: 5180

South Asian (SAS) AF: 0.427 AC: 2058 AN: 4824

European-Finnish (FIN) AF: 0.501 AC: 5300 AN: 10572

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36405 AN: 67954

Other (OTH) AF: 0.436 AC: 921 AN: 2110

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
PhyloP100		-1.5
PromoterAI		0.010	Neutral
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: rs2038978; hg19: chr1-42094719;