1-41581141-C-T

Variant names:

• chr1-41581141-C-T
• rs2810565
• NM_024503.5:c.3657G>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.3657G>A​(p.Gln1219Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 1,548,154 control chromosomes in the GnomAD database, including 768,319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (73060 hom., cov: 29)
  • Exomes 𝑓: 1.0 (695259 hom.)
• Consequence: HIVEP3 NM_024503.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.387
• Publications: 11 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=-0.55).
• BP6: Variant 1-41581141-C-T is Benign according to our data. Variant chr1-41581141-C-T is described in ClinVar as Benign. ClinVar VariationId is 402945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.387 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.3657G>A	p.Gln1219Gln	synonymous	Exon 4 of 9	NP_078779.2	Q5T1R4-1
	HIVEP3	NM_001127714.3		c.3657G>A	p.Gln1219Gln	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.3657G>A	p.Gln1219Gln	synonymous	Exon 4 of 9	ENSP00000361664.1	Q5T1R4-1
	HIVEP3	ENST00000372584.5	TSL:1	c.3657G>A	p.Gln1219Gln	synonymous	Exon 3 of 8	ENSP00000361665.1	Q5T1R4-2
	HIVEP3	ENST00000643665.1		c.3657G>A	p.Gln1219Gln	synonymous	Exon 3 of 8	ENSP00000494598.1	Q5T1R4-2

Frequencies

GnomAD3 genomes AF: 0.980 AC: 148874 AN: 151906 Hom.: 73015 Cov.: 29

Gnomad AFR AF: 0.931

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.992

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.985

GnomAD2 exomes AF: 0.994 AC: 199882 AN: 201080 AF XY: 0.995

Gnomad AFR exome AF: 0.931

Gnomad AMR exome AF: 0.997

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.997

GnomAD4 exome AF: 0.998 AC: 1393219 AN: 1396130 Hom.: 695259 Cov.: 68 AF XY: 0.998 AC XY: 685202 AN XY: 686448

African (AFR) AF: 0.923 AC: 29308 AN: 31736

American (AMR) AF: 0.996 AC: 36880 AN: 37010

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 21574 AN: 21574

East Asian (EAS) AF: 1.00 AC: 39096 AN: 39096

South Asian (SAS) AF: 1.00 AC: 74921 AN: 74928

European-Finnish (FIN) AF: 1.00 AC: 50296 AN: 50296

Middle Eastern (MID) AF: 0.996 AC: 5403 AN: 5426

European-Non Finnish (NFE) AF: 1.00 AC: 1078430 AN: 1078506

Other (OTH) AF: 0.996 AC: 57311 AN: 57558

GnomAD4 genome AF: 0.980 AC: 148977 AN: 152024 Hom.: 73060 Cov.: 29 AF XY: 0.980 AC XY: 72816 AN XY: 74334

African (AFR) AF: 0.931 AC: 38533 AN: 41408

American (AMR) AF: 0.992 AC: 15173 AN: 15290

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5157 AN: 5158

South Asian (SAS) AF: 1.00 AC: 4799 AN: 4800

European-Finnish (FIN) AF: 1.00 AC: 10599 AN: 10600

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 67965 AN: 67984

Other (OTH) AF: 0.985 AC: 2074 AN: 2106

Alfa AF: 0.985 Hom.: 21666

Bravo AF: 0.977

Asia WGS AF: 0.994 AC: 3456 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	-0.55
CADD	Benign	0.48
DANN	Benign	0.36
PhyloP100		0.39
Mutation Taster		=99/1	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: rs2810565; hg19: chr1-42046812; COSMIC: COSV108013030; COSMIC: COSV108013030;