rs137918317

Variant names:

• chr1-41510994-G-A
• rs137918317
• NM_024503.5:c.6678C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_024503.5(HIVEP3):​c.6678C>T​(p.Ser2226Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,613,526 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0067 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (16 hom.)
• Consequence: HIVEP3 NM_024503.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.69
• 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]

ENSG00000295052 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-41510994-G-A is Benign according to our data. Variant chr1-41510994-G-A is described in ClinVar as Benign. ClinVar VariationId is 3039552.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.69 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00668 (1017/152318) while in subpopulation AFR AF = 0.0172 (716/41564). AF 95% confidence interval is 0.0162. There are 6 homozygotes in GnomAd4. There are 551 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 gene

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.6678C>T	p.Ser2226Ser	synonymous	Exon 9 of 9	NP_078779.2	Q5T1R4-1
	HIVEP3	NM_001127714.3		c.6675C>T	p.Ser2225Ser	synonymous	Exon 8 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.6678C>T	p.Ser2226Ser	synonymous	Exon 9 of 9	ENSP00000361664.1	Q5T1R4-1
	HIVEP3	ENST00000372584.5	TSL:1	c.6675C>T	p.Ser2225Ser	synonymous	Exon 8 of 8	ENSP00000361665.1	Q5T1R4-2
	HIVEP3	ENST00000643665.1		c.6675C>T	p.Ser2225Ser	synonymous	Exon 8 of 8	ENSP00000494598.1	Q5T1R4-2

Frequencies

GnomAD3 genomes AF: 0.00664 AC: 1010 AN: 152200 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.0120

Gnomad SAS AF: 0.00993

Gnomad FIN AF: 0.00809

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000970

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00437 AC: 1088 AN: 248708 AF XY: 0.00435

Gnomad AFR exome AF: 0.0168

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00160

Gnomad EAS exome AF: 0.0133

Gnomad FIN exome AF: 0.00613

Gnomad NFE exome AF: 0.00111

Gnomad OTH exome AF: 0.00362

GnomAD4 exome AF: 0.00196 AC: 2868 AN: 1461208 Hom.: 16 Cov.: 34 AF XY: 0.00211 AC XY: 1535 AN XY: 726892

African (AFR) AF: 0.0173 AC: 580 AN: 33474

American (AMR) AF: 0.00121 AC: 54 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00126 AC: 33 AN: 26090

East Asian (EAS) AF: 0.00642 AC: 255 AN: 39696

South Asian (SAS) AF: 0.00840 AC: 724 AN: 86220

European-Finnish (FIN) AF: 0.00546 AC: 290 AN: 53134

Middle Eastern (MID) AF: 0.00850 AC: 49 AN: 5768

European-Non Finnish (NFE) AF: 0.000600 AC: 667 AN: 1111762

Other (OTH) AF: 0.00358 AC: 216 AN: 60376

GnomAD4 genome AF: 0.00668 AC: 1017 AN: 152318 Hom.: 6 Cov.: 32 AF XY: 0.00740 AC XY: 551 AN XY: 74474

African (AFR) AF: 0.0172 AC: 716 AN: 41564

American (AMR) AF: 0.00157 AC: 24 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.0120 AC: 62 AN: 5176

South Asian (SAS) AF: 0.00973 AC: 47 AN: 4830

European-Finnish (FIN) AF: 0.00809 AC: 86 AN: 10628

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000956 AC: 65 AN: 68020

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00262 Hom.: 0

Bravo AF: 0.00636

Asia WGS AF: 0.0150 AC: 51 AN: 3478

EpiCase AF: 0.000763

EpiControl AF: 0.000830

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	HIVEP3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.099
DANN	Benign	0.74
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs137918317; hg19: chr1-41976665; COSMIC: COSV107210721;