6-12122540-T-C

Variant names:

• chr6-12122540-T-C
• rs2228211
• NM_002114.4:c.2745T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002114.4(HIVEP1):​c.2745T>C​(p.Thr915Thr) 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.589
• Publications: 13 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 -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 VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIVEP1	NM_002114.4	MANE Select	c.2745T>C	p.Thr915Thr	synonymous	Exon 4 of 9	NP_002105.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIVEP1	ENST00000379388.7	TSL:1 MANE Select	c.2745T>C	p.Thr915Thr	synonymous	Exon 4 of 9	ENSP00000368698.2
	HIVEP1	ENST00000478545.2	TSL:4	c.2745T>C	p.Thr915Thr	synonymous	Exon 4 of 9	ENSP00000418021.2
	HIVEP1	ENST00000487103.6	TSL:2	c.2745T>C	p.Thr915Thr	synonymous	Exon 4 of 9	ENSP00000417348.2

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29427 AN: 152052 Hom.: 3235 Cov.: 32

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

GnomAD2 exomes AF: 0.239 AC: 59653 AN: 249294 AF XY: 0.239

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 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.: 46 AF XY: 0.213 AC XY: 154984 AN XY: 727210

African (AFR) AF: 0.110 AC: 3671 AN: 33478

American (AMR) AF: 0.307 AC: 13710 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 4297 AN: 26136

East Asian (EAS) AF: 0.438 AC: 17399 AN: 39698

South Asian (SAS) AF: 0.290 AC: 24980 AN: 86256

European-Finnish (FIN) AF: 0.231 AC: 12360 AN: 53412

Middle Eastern (MID) AF: 0.176 AC: 1014 AN: 5768

European-Non Finnish (NFE) AF: 0.197 AC: 218949 AN: 1111962

Other (OTH) AF: 0.219 AC: 13211 AN: 60392

GnomAD4 genome AF: 0.194 AC: 29463 AN: 152170 Hom.: 3248 Cov.: 32 AF XY: 0.200 AC XY: 14853 AN XY: 74382

African (AFR) AF: 0.113 AC: 4713 AN: 41542

American (AMR) AF: 0.249 AC: 3807 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 572 AN: 3472

East Asian (EAS) AF: 0.469 AC: 2424 AN: 5172

South Asian (SAS) AF: 0.298 AC: 1434 AN: 4814

European-Finnish (FIN) AF: 0.243 AC: 2566 AN: 10576

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13280 AN: 67984

Other (OTH) AF: 0.184 AC: 389 AN: 2112

Alfa AF: 0.192 Hom.: 3130

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

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.46
DANN	Benign	0.34
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

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: rs2228211; hg19: chr6-12122773; COSMIC: COSV65106142; COSMIC: COSV65106142;