chr1-41510659-G-A

Variant names:

• chr1-41510659-G-A
• rs58930436
• NM_024503.5:c.7013C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_024503.5(HIVEP3):​c.7013C>T​(p.Pro2338Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00504 in 1,526,972 control chromosomes in the GnomAD database, including 330 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Synonymous variant affecting the same amino acid position (i.e. P2338P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.026 (183 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (147 hom.)
• Consequence: HIVEP3 NM_024503.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.188
• Publications: 3 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024409592).
• BP6: Variant 1-41510659-G-A is Benign according to our data. Variant chr1-41510659-G-A is described in ClinVar as Benign. ClinVar VariationId is 3037301.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0878 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.7013C>T	p.Pro2338Leu	missense	Exon 9 of 9	NP_078779.2	Q5T1R4-1
	HIVEP3	NM_001127714.3		c.7010C>T	p.Pro2337Leu	missense	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.7013C>T	p.Pro2338Leu	missense	Exon 9 of 9	ENSP00000361664.1	Q5T1R4-1
	HIVEP3	ENST00000372584.5	TSL:1	c.7010C>T	p.Pro2337Leu	missense	Exon 8 of 8	ENSP00000361665.1	Q5T1R4-2
	HIVEP3	ENST00000643665.1		c.7010C>T	p.Pro2337Leu	missense	Exon 8 of 8	ENSP00000494598.1	Q5T1R4-2

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 3956 AN: 152162 Hom.: 183 Cov.: 33

Gnomad AFR AF: 0.0904

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00929

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0234

GnomAD2 exomes AF: 0.00618 AC: 834 AN: 135002 AF XY: 0.00505

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.00290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000366

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000318

Gnomad OTH exome AF: 0.00205

GnomAD4 exome AF: 0.00272 AC: 3737 AN: 1374692 Hom.: 147 Cov.: 34 AF XY: 0.00238 AC XY: 1608 AN XY: 675394

African (AFR) AF: 0.0958 AC: 2986 AN: 31172

American (AMR) AF: 0.00384 AC: 132 AN: 34374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24118

East Asian (EAS) AF: 0.000197 AC: 7 AN: 35498

South Asian (SAS) AF: 0.000710 AC: 55 AN: 77438

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42936

Middle Eastern (MID) AF: 0.00213 AC: 10 AN: 4702

European-Non Finnish (NFE) AF: 0.000223 AC: 238 AN: 1067572

Other (OTH) AF: 0.00543 AC: 309 AN: 56882

GnomAD4 genome AF: 0.0260 AC: 3961 AN: 152280 Hom.: 183 Cov.: 33 AF XY: 0.0257 AC XY: 1914 AN XY: 74470

African (AFR) AF: 0.0902 AC: 3749 AN: 41542

American (AMR) AF: 0.00928 AC: 142 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68000

Other (OTH) AF: 0.0232 AC: 49 AN: 2114

Alfa AF: 0.00402 Hom.: 6

Bravo AF: 0.0300

ESP6500AA AF: 0.0679 AC: 273

ESP6500EA AF: 0.000644 AC: 5

ExAC AF: 0.00638 AC: 664

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions

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
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.020
DANN	Benign	0.42
DEOGEN2	Benign	0.077	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0046	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.46	N
PhyloP100		0.19
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.032
Sift	Benign	1.0	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.032
MVP		0.055
MPC		0.19
ClinPred		0.0014	T
GERP RS		-5.5
Varity_R		0.025
gMVP		0.028
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: rs58930436; hg19: chr1-41976330;