rs149594953

Variant names:

• chr6-12120057-C-T
• rs149594953
• NM_002114.4:c.262C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002114.4(HIVEP1):​c.262C>T​(p.His88Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000451 in 1,613,310 control chromosomes in the GnomAD database, including 1 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (1 hom.)
• Consequence: HIVEP1 NM_002114.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.58
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038490891).
• BP6: Variant 6-12120057-C-T is Benign according to our data. Variant chr6-12120057-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 785158.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 399 AD gene.

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.262C>T	p.His88Tyr	missense	Exon 4 of 9	NP_002105.3	P15822-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIVEP1	ENST00000379388.7	TSL:1 MANE Select	c.262C>T	p.His88Tyr	missense	Exon 4 of 9	ENSP00000368698.2	P15822-1
	HIVEP1	ENST00000478545.2	TSL:4	c.262C>T	p.His88Tyr	missense	Exon 4 of 9	ENSP00000418021.2	P15822-1
	HIVEP1	ENST00000487103.6	TSL:2	c.262C>T	p.His88Tyr	missense	Exon 4 of 9	ENSP00000417348.2	P15822-1

Frequencies

GnomAD3 genomes AF: 0.00262 AC: 399 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00922

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000599 AC: 149 AN: 248554 AF XY: 0.000438

Gnomad AFR exome AF: 0.00873

Gnomad AMR exome AF: 0.000321

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000224 AC: 328 AN: 1461044 Hom.: 1 Cov.: 33 AF XY: 0.000191 AC XY: 139 AN XY: 726796

African (AFR) AF: 0.00851 AC: 284 AN: 33366

American (AMR) AF: 0.000292 AC: 13 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111790

Other (OTH) AF: 0.000431 AC: 26 AN: 60364

GnomAD4 genome AF: 0.00262 AC: 399 AN: 152266 Hom.: 0 Cov.: 32 AF XY: 0.00257 AC XY: 191 AN XY: 74442

African (AFR) AF: 0.00919 AC: 382 AN: 41546

American (AMR) AF: 0.000589 AC: 9 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68024

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00118 Hom.: 0

Bravo AF: 0.00308

ESP6500AA AF: 0.00872 AC: 32

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.000712 AC: 86

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.3
DANN	Benign	0.95
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.6
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.074
Sift	Benign	0.15	T
Sift4G	Benign	0.42	T
Vest4		0.10
MVP		0.13
MPC		0.14
ClinPred		0.020	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.048
Mutation Taster		=94/6	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: rs149594953; hg19: chr6-12120290;