Variant 6-12122540-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002114.4(HIVEP1):c.2745T>C(p.Thr915=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,613,990 control chromosomes in the GnomAD database, including 38,171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.19 ( 3248 hom., cov: 32)

Exomes 𝑓: 0.21 ( 34923 hom. )

Consequence

HIVEP1
NM_002114.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.589

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 6-12122540-T-C is Benign according to our data. Variant chr6-12122540-T-C is described in ClinVar as [Benign]. Clinvar id is 402935.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIVEP1	NM_002114.4 linkuse as main transcript	c.2745T>C	p.Thr915=	synonymous_variant	4/9	ENST00000379388.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIVEP1	ENST00000379388.7 linkuse as main transcript	c.2745T>C	p.Thr915=	synonymous_variant	4/9	1	NM_002114.4	P2	P15822-1
HIVEP1	ENST00000541134.5 linkuse as main transcript	c.2745T>C	p.Thr915=	synonymous_variant	4/9	5		A2
HIVEP1	ENST00000627968.2 linkuse as main transcript	c.-3559T>C		5_prime_UTR_variant	4/8	5
HIVEP1	ENST00000442081.6 linkuse as main transcript	c.166+2606T>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29427

AN:

152052

Hom.:

3235

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.263

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.468

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.181

GnomAD3 exomes

AF:

0.239

AC:

59653

AN:

249294

Hom.:

8248

AF XY:

0.239

AC XY:

32270

AN XY:

135256

show subpopulations

Gnomad AFR exome

AF:

0.111

Gnomad AMR exome

AF:

0.312

Gnomad ASJ exome

AF:

0.169

Gnomad EAS exome

AF:

0.478

Gnomad SAS exome

AF:

0.292

Gnomad FIN exome

AF:

0.231

Gnomad NFE exome

AF:

0.191

Gnomad OTH exome

AF:

0.235

GnomAD4 exome

AF:

0.212

AC:

309591

AN:

1461820

Hom.:

34923

Cov.:

AF XY:

0.213

AC XY:

154984

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.307

Gnomad4 ASJ exome

AF:

0.164

Gnomad4 EAS exome

AF:

0.438

Gnomad4 SAS exome

AF:

0.290

Gnomad4 FIN exome

AF:

0.231

Gnomad4 NFE exome

AF:

0.197

Gnomad4 OTH exome

AF:

0.219

GnomAD4 genome

AF:

0.194

AC:

29463

AN:

152170

Hom.:

3248

Cov.:

AF XY:

0.200

AC XY:

14853

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.113

Gnomad4 AMR

AF:

0.249

Gnomad4 ASJ

AF:

0.165

Gnomad4 EAS

AF:

0.469

Gnomad4 SAS

AF:

0.298

Gnomad4 FIN

AF:

0.243

Gnomad4 NFE

AF:

0.195

Gnomad4 OTH

AF:

0.184

Alfa

AF:

0.193

Hom.:

2820

Bravo

AF:

0.192

Asia WGS

AF:

0.344

AC:

1196

AN:

3478

EpiCase

AF:

0.187

EpiControl

AF:

0.183

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

Cadd

Benign

0.46

Dann

Benign

0.34

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

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