rs61738287

Variant names:

• chr6-12120303-A-G
• rs61738287
• NM_002114.4:c.508A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_002114.4(HIVEP1):​c.508A>G​(p.Ser170Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00223 in 1,614,168 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (32 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (41 hom.)
• Consequence: HIVEP1 NM_002114.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.642
• Publications: 4 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.

• BP6: Variant 6-12120303-A-G is Benign according to our data. Variant chr6-12120303-A-G is described in ClinVar as Benign. ClinVar VariationId is 708913.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0116 (1763/152322) while in subpopulation AFR AF = 0.0399 (1659/41564). AF 95% confidence interval is 0.0383. There are 32 homozygotes in GnomAd4. There are 826 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1763 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.508A>G	p.Ser170Gly	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.508A>G	p.Ser170Gly	missense	Exon 4 of 9	ENSP00000368698.2	P15822-1
	HIVEP1	ENST00000478545.2	TSL:4	c.508A>G	p.Ser170Gly	missense	Exon 4 of 9	ENSP00000418021.2	P15822-1
	HIVEP1	ENST00000487103.6	TSL:2	c.508A>G	p.Ser170Gly	missense	Exon 4 of 9	ENSP00000417348.2	P15822-1

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1759 AN: 152204 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.0400

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00300 AC: 747 AN: 249362 AF XY: 0.00205

Gnomad AFR exome AF: 0.0423

Gnomad AMR exome AF: 0.00183

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000992

GnomAD4 exome AF: 0.00126 AC: 1835 AN: 1461846 Hom.: 41 Cov.: 39 AF XY: 0.00108 AC XY: 785 AN XY: 727226

African (AFR) AF: 0.0440 AC: 1474 AN: 33480

American (AMR) AF: 0.00210 AC: 94 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000278 AC: 24 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5768

European-Non Finnish (NFE) AF: 0.0000612 AC: 68 AN: 1111988

Other (OTH) AF: 0.00255 AC: 154 AN: 60394

GnomAD4 genome AF: 0.0116 AC: 1763 AN: 152322 Hom.: 32 Cov.: 32 AF XY: 0.0111 AC XY: 826 AN XY: 74494

African (AFR) AF: 0.0399 AC: 1659 AN: 41564

American (AMR) AF: 0.00484 AC: 74 AN: 15304

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

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

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68030

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

Alfa AF: 0.00465 Hom.: 20

Bravo AF: 0.0137

ESP6500AA AF: 0.0378 AC: 156

ESP6500EA AF: 0.000237 AC: 2

ExAC AF: 0.00353 AC: 427

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: 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	0.063
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.97
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.94	T
PhyloP100		0.64
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.067
Sift	Benign	0.088	T
Sift4G	Benign	0.18	T
Vest4		0.088
MVP		0.46
MPC		0.082
ClinPred		0.0043	T
GERP RS		0.59
gMVP		0.080
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.42		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs61738287; hg19: chr6-12120536;