chr6-12125539-A-G

Variant names:

• chr6-12125539-A-G
• rs1126472
• NM_002114.4:c.5744A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002114.4(HIVEP1):​c.5744A>G​(p.Gln1915Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,972 control chromosomes in the GnomAD database, including 11,695 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1769 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9926 hom.)
• Consequence: HIVEP1 NM_002114.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.18
• Publications: 21 publications found

Genes affected

HIVEP1 (HGNC:4920): (HIVEP zinc finger 1) This gene encodes a transcription factor belonging to the ZAS family, members of which are large proteins that contain a ZAS domain - a modular protein structure consisting of a pair of C2H2 zinc fingers with an acidic-rich region and a serine/threonine-rich sequence. These proteins bind specifically to the DNA sequence motif, GGGACTTTCC, found in the enhancer elements of several viral promoters, including human immunodeficiency virus (HIV), and to related sequences found in the enhancer elements of a number of cellular promoters. This protein binds to this sequence motif, suggesting a role in the transcriptional regulation of both viral and cellular genes. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005001366).
• BP6: Variant 6-12125539-A-G is Benign according to our data. Variant chr6-12125539-A-G is described in ClinVar as Benign. ClinVar VariationId is 402938.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002114.4. 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
	HIVEP1	NM_002114.4	MANE Select	c.5744A>G	p.Gln1915Arg	missense	Exon 4 of 9	NP_002105.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIVEP1	ENST00000379388.7	TSL:1 MANE Select	c.5744A>G	p.Gln1915Arg	missense	Exon 4 of 9	ENSP00000368698.2
	HIVEP1	ENST00000478545.2	TSL:4	c.5744A>G	p.Gln1915Arg	missense	Exon 4 of 9	ENSP00000418021.2
	HIVEP1	ENST00000487103.6	TSL:2	c.5744A>G	p.Gln1915Arg	missense	Exon 4 of 9	ENSP00000417348.2

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21238 AN: 152156 Hom.: 1759 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.0550

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.164

GnomAD2 exomes AF: 0.120 AC: 29823 AN: 249166 AF XY: 0.122

Gnomad AFR exome AF: 0.223

Gnomad AMR exome AF: 0.0882

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.125

Gnomad FIN exome AF: 0.0596

Gnomad NFE exome AF: 0.109

Gnomad OTH exome AF: 0.124

GnomAD4 exome AF: 0.111 AC: 162252 AN: 1461698 Hom.: 9926 Cov.: 34 AF XY: 0.113 AC XY: 82376 AN XY: 727170

African (AFR) AF: 0.221 AC: 7410 AN: 33474

American (AMR) AF: 0.0915 AC: 4092 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 3595 AN: 26130

East Asian (EAS) AF: 0.110 AC: 4349 AN: 39696

South Asian (SAS) AF: 0.172 AC: 14852 AN: 86250

European-Finnish (FIN) AF: 0.0605 AC: 3229 AN: 53400

Middle Eastern (MID) AF: 0.223 AC: 1287 AN: 5768

European-Non Finnish (NFE) AF: 0.104 AC: 115707 AN: 1111862

Other (OTH) AF: 0.128 AC: 7731 AN: 60394

GnomAD4 genome AF: 0.140 AC: 21283 AN: 152274 Hom.: 1769 Cov.: 32 AF XY: 0.138 AC XY: 10247 AN XY: 74458

African (AFR) AF: 0.219 AC: 9099 AN: 41540

American (AMR) AF: 0.123 AC: 1877 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 474 AN: 3466

East Asian (EAS) AF: 0.122 AC: 634 AN: 5188

South Asian (SAS) AF: 0.173 AC: 835 AN: 4828

European-Finnish (FIN) AF: 0.0550 AC: 584 AN: 10616

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.107 AC: 7284 AN: 68016

Other (OTH) AF: 0.162 AC: 341 AN: 2110

Alfa AF: 0.123 Hom.: 3599

Bravo AF: 0.147

TwinsUK AF: 0.103 AC: 381

ALSPAC AF: 0.104 AC: 401

ESP6500AA AF: 0.205 AC: 789

ESP6500EA AF: 0.100 AC: 823

ExAC AF: 0.123 AC: 14885

Asia WGS AF: 0.175 AC: 608 AN: 3478

EpiCase AF: 0.115

EpiControl AF: 0.119

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.0050
DANN	Benign	0.15
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.14	T
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-0.91	T
PhyloP100		-3.2
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.015
Sift	Benign	0.56	T
Sift4G	Benign	0.54	T
Vest4		0.0020
MPC		0.092
ClinPred		0.00030	T
GERP RS		-6.6
gMVP		0.15
Mutation Taster		=100/0	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: rs1126472; hg19: chr6-12125772; COSMIC: COSV65101833; COSMIC: COSV65101833;