Variant 6-12120303-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

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. 12/20 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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.642

Variant links:

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]

HIVEP1 links:

HIVEP1 (HGNC:):

HIVEP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1763 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIVEP1	NM_002114.4 linkuse as main transcript	c.508A>G	p.Ser170Gly	missense_variant	4/9	ENST00000379388.7	NP_002105.3	P15822-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HIVEP1	ENST00000379388.7 linkuse as main transcript	c.508A>G	p.Ser170Gly	missense_variant	4/9	1	NM_002114.4	ENSP00000368698.2	P15822-1
HIVEP1	ENST00000541134.5 linkuse as main transcript	c.508A>G	p.Ser170Gly	missense_variant	4/9	5			F5H212
HIVEP1	ENST00000627968 linkuse as main transcript	c.-5796A>G		5_prime_UTR_variant	4/8	5		ENSP00000486543.2	A0A0D9SFF3
HIVEP1	ENST00000442081.6 linkuse as main transcript	c.166+369A>G		intron_variant		3		ENSP00000409078.3	C9JLG1

Frequencies

GnomAD3 genomes

AF:

0.0116

AC:

1759

AN:

152204

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00300

AC:

747

AN:

249362

Hom.:

AF XY:

0.00205

AC XY:

278

AN XY:

135284

show subpopulations

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 SAS exome

AF:

0.000360

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.:

Cov.:

AF XY:

0.00108

AC XY:

785

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0440

Gnomad4 AMR exome

AF:

0.00210

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000612

Gnomad4 OTH exome

AF:

0.00255

GnomAD4 genome

AF:

0.0116

AC:

1763

AN:

152322

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

826

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0399

Gnomad4 AMR

AF:

0.00484

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.00199

Hom.:

Bravo

AF:

0.0137

ESP6500AA

AF:

0.0378

AC:

156

ESP6500EA

AF:

0.000237

AC:

ExAC

AF:

0.00353

AC:

427

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.61

T;.

MetaRNN

Benign

0.0028

T;T

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.95

.;N

REVEL

Benign

0.067

Sift

Benign

0.088

.;T

Sift4G

Benign

0.18

T;T

Vest4

0.088

MVP

0.46

MPC

0.082

ClinPred

0.0043

GERP RS

0.59

gMVP

0.080

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over