chr6-12121941-A-G

Position:

• chr6-12121941-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000379388.7(HIVEP1):​c.2146A>G​(p.Thr716Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,613,794 control chromosomes in the GnomAD database, including 90,091 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T716M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.26 (6163 hom., cov: 32)
  • Exomes 𝑓: 0.33 (83928 hom.)
• Consequence: HIVEP1 ENST00000379388.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003978461).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIVEP1	NM_002114.4	c.2146A>G	p.Thr716Ala	missense_variant	4/9	ENST00000379388.7	NP_002105.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIVEP1	ENST00000379388.7	c.2146A>G	p.Thr716Ala	missense_variant	4/9	1	NM_002114.4	ENSP00000368698.2
HIVEP1	ENST00000541134.5	c.2146A>G	p.Thr716Ala	missense_variant	4/9	5
HIVEP1	ENST00000627968	c.-4158A>G		5_prime_UTR_variant	4/8	5		ENSP00000486543.2
HIVEP1	ENST00000442081.6	c.166+2007A>G		intron_variant		3		ENSP00000409078.3

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39066 AN: 151946 Hom.: 6171 Cov.: 32

Gnomad AFR AF: 0.0678

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.277

GnomAD3 exomes AF: 0.301 AC: 74911 AN: 248896 Hom.: 12260 AF XY: 0.307 AC XY: 41541 AN XY: 135094

Gnomad AFR exome AF: 0.0609

Gnomad AMR exome AF: 0.242

Gnomad ASJ exome AF: 0.343

Gnomad EAS exome AF: 0.233

Gnomad SAS exome AF: 0.272

Gnomad FIN exome AF: 0.348

Gnomad NFE exome AF: 0.357

Gnomad OTH exome AF: 0.320

GnomAD4 exome AF: 0.334 AC: 488143 AN: 1461730 Hom.: 83928 Cov.: 47 AF XY: 0.333 AC XY: 242491 AN XY: 727160

Gnomad4 AFR exome AF: 0.0560

Gnomad4 AMR exome AF: 0.245

Gnomad4 ASJ exome AF: 0.353

Gnomad4 EAS exome AF: 0.256

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.344

Gnomad4 NFE exome AF: 0.354

Gnomad4 OTH exome AF: 0.315

GnomAD4 genome AF: 0.257 AC: 39045 AN: 152064 Hom.: 6163 Cov.: 32 AF XY: 0.254 AC XY: 18878 AN XY: 74298

Gnomad4 AFR AF: 0.0677

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.278

Alfa AF: 0.336 Hom.: 23073

Bravo AF: 0.248

TwinsUK AF: 0.361 AC: 1340

ALSPAC AF: 0.347 AC: 1336

ESP6500AA AF: 0.0657 AC: 274

ESP6500EA AF: 0.350 AC: 2940

ExAC AF: 0.299 AC: 36244

Asia WGS AF: 0.253 AC: 877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.060
DANN	Benign	0.31
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.34	T;.
MetaRNN	Benign	0.0040	T;T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.90	.;N
REVEL	Benign	0.027
Sift	Benign	0.36	.;T
Sift4G	Benign	0.50	T;T
Vest4		0.015
MPC		0.084
ClinPred		0.013	T
GERP RS		-7.6
gMVP		0.17

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

Other links and lift over

dbSNP: rs2228210; hg19: chr6-12122174; COSMIC: COSV65101743; COSMIC: COSV65101743;