chr1-41510950-C-T

Variant names:

• chr1-41510950-C-T
• rs147749727
• NM_024503.5:c.6722G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_024503.5(HIVEP3):​c.6722G>A​(p.Arg2241Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,613,586 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0022 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (12 hom.)
• Consequence: HIVEP3 NM_024503.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.459
• Publications: 7 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00291574).
• BP6: Variant 1-41510950-C-T is Benign according to our data. Variant chr1-41510950-C-T is described in ClinVar as Benign. ClinVar VariationId is 3039451.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 5 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.6722G>A	p.Arg2241Gln	missense	Exon 9 of 9	NP_078779.2	Q5T1R4-1
	HIVEP3	NM_001127714.3		c.6719G>A	p.Arg2240Gln	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.6722G>A	p.Arg2241Gln	missense	Exon 9 of 9	ENSP00000361664.1	Q5T1R4-1
	HIVEP3	ENST00000372584.5	TSL:1	c.6719G>A	p.Arg2240Gln	missense	Exon 8 of 8	ENSP00000361665.1	Q5T1R4-2
	HIVEP3	ENST00000643665.1		c.6719G>A	p.Arg2240Gln	missense	Exon 8 of 8	ENSP00000494598.1	Q5T1R4-2

Frequencies

GnomAD3 genomes AF: 0.00221 AC: 337 AN: 152188 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000844

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.0112

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00246

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00222 AC: 554 AN: 249834 AF XY: 0.00218

Gnomad AFR exome AF: 0.000874

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.000200

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0114

Gnomad NFE exome AF: 0.00195

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00146 AC: 2130 AN: 1461280 Hom.: 12 Cov.: 34 AF XY: 0.00154 AC XY: 1122 AN XY: 726944

African (AFR) AF: 0.000926 AC: 31 AN: 33470

American (AMR) AF: 0.000179 AC: 8 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00233 AC: 201 AN: 86252

European-Finnish (FIN) AF: 0.00952 AC: 505 AN: 53034

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00116 AC: 1294 AN: 1111854

Other (OTH) AF: 0.00144 AC: 87 AN: 60374

GnomAD4 genome AF: 0.00221 AC: 337 AN: 152306 Hom.: 5 Cov.: 32 AF XY: 0.00255 AC XY: 190 AN XY: 74472

African (AFR) AF: 0.000842 AC: 35 AN: 41570

American (AMR) AF: 0.000131 AC: 2 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4822

European-Finnish (FIN) AF: 0.0112 AC: 119 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00246 AC: 167 AN: 68010

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00192 Hom.: 3

Bravo AF: 0.00111

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00221 AC: 19

ExAC AF: 0.00218 AC: 265

EpiCase AF: 0.00164

EpiControl AF: 0.00119

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	0.076
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.62
CADD	Uncertain	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.46
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.026
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.12	T
Polyphen		0.012	B
Vest4		0.082
MVP		0.20
MPC		0.22
ClinPred		0.060	T
GERP RS		3.3
Varity_R		0.12
gMVP		0.18
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: rs147749727; hg19: chr1-41976621; COSMIC: COSV56011535;