rs2984694

Variant names:

• chr1-41583361-G-A
• rs2984694
• NM_024503.5:c.1437C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-41583361-G-A
• chr1-41583361-G-C

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.1437C>T​(p.Ser479Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.992 in 1,612,766 control chromosomes in the GnomAD database, including 794,395 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (70096 hom., cov: 29)
  • Exomes 𝑓: 1.0 (724299 hom.)
• Consequence: HIVEP3 NM_024503.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.366
• 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=-0.54).
• BP6: Variant 1-41583361-G-A is Benign according to our data. Variant chr1-41583361-G-A is described in ClinVar as Benign. ClinVar VariationId is 402946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.366 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.1437C>T	p.Ser479Ser	synonymous	Exon 4 of 9	NP_078779.2	Q5T1R4-1
	HIVEP3	NM_001127714.3		c.1437C>T	p.Ser479Ser	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.1437C>T	p.Ser479Ser	synonymous	Exon 4 of 9	ENSP00000361664.1	Q5T1R4-1
	HIVEP3	ENST00000372584.5	TSL:1	c.1437C>T	p.Ser479Ser	synonymous	Exon 3 of 8	ENSP00000361665.1	Q5T1R4-2
	HIVEP3	ENST00000643665.1		c.1437C>T	p.Ser479Ser	synonymous	Exon 3 of 8	ENSP00000494598.1	Q5T1R4-2

Frequencies

GnomAD3 genomes AF: 0.958 AC: 145593 AN: 152026 Hom.: 70054 Cov.: 29

Gnomad AFR AF: 0.852

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.986

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.968

GnomAD2 exomes AF: 0.989 AC: 247800 AN: 250492 AF XY: 0.992

Gnomad AFR exome AF: 0.852

Gnomad AMR exome AF: 0.994

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: 0.996

GnomAD4 exome AF: 0.996 AC: 1454167 AN: 1460622 Hom.: 724299 Cov.: 67 AF XY: 0.996 AC XY: 723665 AN XY: 726454

African (AFR) AF: 0.842 AC: 28173 AN: 33468

American (AMR) AF: 0.993 AC: 44319 AN: 44648

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26068 AN: 26068

East Asian (EAS) AF: 1.00 AC: 39672 AN: 39672

South Asian (SAS) AF: 1.00 AC: 86025 AN: 86046

European-Finnish (FIN) AF: 1.00 AC: 53366 AN: 53366

Middle Eastern (MID) AF: 0.992 AC: 5717 AN: 5766

European-Non Finnish (NFE) AF: 1.00 AC: 1111079 AN: 1111262

Other (OTH) AF: 0.990 AC: 59748 AN: 60326

GnomAD4 genome AF: 0.958 AC: 145692 AN: 152144 Hom.: 70096 Cov.: 29 AF XY: 0.958 AC XY: 71267 AN XY: 74374

African (AFR) AF: 0.852 AC: 35343 AN: 41484

American (AMR) AF: 0.986 AC: 15089 AN: 15300

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

East Asian (EAS) AF: 1.00 AC: 5120 AN: 5120

South Asian (SAS) AF: 0.999 AC: 4811 AN: 4814

European-Finnish (FIN) AF: 1.00 AC: 10614 AN: 10614

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

European-Non Finnish (NFE) AF: 1.00 AC: 67996 AN: 68026

Other (OTH) AF: 0.969 AC: 2042 AN: 2108

Alfa AF: 0.984 Hom.: 116462

Bravo AF: 0.952

Asia WGS AF: 0.990 AC: 3442 AN: 3478

EpiCase AF: 1.00

EpiControl AF: 1.00

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	-0.54
CADD	Benign	1.5
DANN	Benign	0.82
PhyloP100		0.37
Mutation Taster		=98/2	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: rs2984694; hg19: chr1-42049032; COSMIC: COSV56020329; COSMIC: COSV56020329;