chr1-41583469-C-T

Variant names:

• chr1-41583469-C-T
• rs2475842
• NM_024503.5:c.1329G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_024503.5(HIVEP3):​c.1329G>A​(p.Leu443Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L443L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 29)
• Consequence: HIVEP3 NM_024503.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334
• Publications: 10 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=0.334 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIVEP3	NM_024503.5	c.1329G>A	p.Leu443Leu	synonymous_variant	Exon 4 of 9	ENST00000372583.6	NP_078779.2
HIVEP3	NM_001127714.3	c.1329G>A	p.Leu443Leu	synonymous_variant	Exon 3 of 8		NP_001121186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIVEP3	ENST00000372583.6	c.1329G>A	p.Leu443Leu	synonymous_variant	Exon 4 of 9	1	NM_024503.5	ENSP00000361664.1
HIVEP3	ENST00000372584.5	c.1329G>A	p.Leu443Leu	synonymous_variant	Exon 3 of 8	1		ENSP00000361665.1
HIVEP3	ENST00000643665.1	c.1329G>A	p.Leu443Leu	synonymous_variant	Exon 3 of 8			ENSP00000494598.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 68

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.8
DANN	Benign	0.75
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism

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: rs2475842; hg19: chr1-42049140;