rs12132697

Variant names:

• chr1-41580942-G-T
• rs12132697
• NM_024503.5:c.3856C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-41580942-G-T
• chr1-41580942-G-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_024503.5(HIVEP3):​c.3856C>A​(p.Arg1286Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,611,188 control chromosomes in the GnomAD database, including 48,896 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (3079 hom., cov: 33)
  • Exomes 𝑓: 0.24 (45817 hom.)
• Consequence: HIVEP3 NM_024503.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.83
• Publications: 12 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]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 1-41580942-G-T is Benign according to our data. Variant chr1-41580942-G-T is described in ClinVar as Benign. ClinVar VariationId is 402944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.83 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024503.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIVEP3	NM_024503.5	MANE Select	c.3856C>A	p.Arg1286Arg	synonymous	Exon 4 of 9	NP_078779.2	Q5T1R4-1
	HIVEP3	NM_001127714.3		c.3856C>A	p.Arg1286Arg	synonymous	Exon 3 of 8	NP_001121186.1	Q5T1R4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIVEP3	ENST00000372583.6	TSL:1 MANE Select	c.3856C>A	p.Arg1286Arg	synonymous	Exon 4 of 9	ENSP00000361664.1	Q5T1R4-1
	HIVEP3	ENST00000372584.5	TSL:1	c.3856C>A	p.Arg1286Arg	synonymous	Exon 3 of 8	ENSP00000361665.1	Q5T1R4-2
	HIVEP3	ENST00000643665.1		c.3856C>A	p.Arg1286Arg	synonymous	Exon 3 of 8	ENSP00000494598.1	Q5T1R4-2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27498 AN: 152034 Hom.: 3079 Cov.: 33

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0484

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.173

GnomAD2 exomes AF: 0.190 AC: 46940 AN: 247584 AF XY: 0.196

Gnomad AFR exome AF: 0.0487

Gnomad AMR exome AF: 0.0981

Gnomad ASJ exome AF: 0.167

Gnomad EAS exome AF: 0.0479

Gnomad FIN exome AF: 0.231

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.201

GnomAD4 exome AF: 0.243 AC: 354134 AN: 1459038 Hom.: 45817 Cov.: 44 AF XY: 0.241 AC XY: 174809 AN XY: 725536

African (AFR) AF: 0.0436 AC: 1458 AN: 33464

American (AMR) AF: 0.104 AC: 4639 AN: 44496

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 4279 AN: 25896

East Asian (EAS) AF: 0.0605 AC: 2402 AN: 39690

South Asian (SAS) AF: 0.179 AC: 15360 AN: 85616

European-Finnish (FIN) AF: 0.228 AC: 12099 AN: 53100

Middle Eastern (MID) AF: 0.159 AC: 913 AN: 5754

European-Non Finnish (NFE) AF: 0.270 AC: 299387 AN: 1110762

Other (OTH) AF: 0.226 AC: 13597 AN: 60260

GnomAD4 genome AF: 0.181 AC: 27485 AN: 152150 Hom.: 3079 Cov.: 33 AF XY: 0.177 AC XY: 13163 AN XY: 74396

African (AFR) AF: 0.0558 AC: 2319 AN: 41534

American (AMR) AF: 0.142 AC: 2172 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 595 AN: 3470

East Asian (EAS) AF: 0.0485 AC: 251 AN: 5170

South Asian (SAS) AF: 0.181 AC: 872 AN: 4818

European-Finnish (FIN) AF: 0.235 AC: 2491 AN: 10582

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18057 AN: 67966

Other (OTH) AF: 0.171 AC: 360 AN: 2110

Alfa AF: 0.207 Hom.: 2636

Bravo AF: 0.167

Asia WGS AF: 0.129 AC: 451 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	HIVEP3-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	3.8
DANN	Benign	0.59
PhyloP100		1.8
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: rs12132697; hg19: chr1-42046613; COSMIC: COSV56021960; COSMIC: COSV56021960;