rs2228212

Variant names:

• chr6-12124354-C-G
• rs2228212
• NM_002114.4:c.4559C>G
• HIVEP1 p.Ala1520Gly

Your query was ambiguous. Multiple possible variants found:

• chr6-12124354-C-G
• chr6-12124354-C-T

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.4559C>G​(p.Ala1520Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 1,613,108 control chromosomes in the GnomAD database, including 96,623 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (7692 hom., cov: 32)
  • Exomes 𝑓: 0.35 (88931 hom.)
• Consequence: HIVEP1 NM_002114.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.702
• Publications: 22 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 (MetaRNN=0.0028498769).
• BP6: Variant 6-12124354-C-G is Benign according to our data. Variant chr6-12124354-C-G is described in ClinVar as Benign. ClinVar VariationId is 402937.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.357 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIVEP1	NM_002114.4	MANE Select	c.4559C>G	p.Ala1520Gly	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.4559C>G	p.Ala1520Gly	missense	Exon 4 of 9	ENSP00000368698.2	P15822-1
	HIVEP1	ENST00000478545.2	TSL:4	c.4559C>G	p.Ala1520Gly	missense	Exon 4 of 9	ENSP00000418021.2	P15822-1
	HIVEP1	ENST00000487103.6	TSL:2	c.4559C>G	p.Ala1520Gly	missense	Exon 4 of 9	ENSP00000417348.2	P15822-1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47254 AN: 151910 Hom.: 7693 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.320

GnomAD2 exomes AF: 0.324 AC: 80788 AN: 249220 AF XY: 0.323

Gnomad AFR exome AF: 0.219

Gnomad AMR exome AF: 0.357

Gnomad ASJ exome AF: 0.360

Gnomad EAS exome AF: 0.165

Gnomad FIN exome AF: 0.363

Gnomad NFE exome AF: 0.358

Gnomad OTH exome AF: 0.332

GnomAD4 exome AF: 0.346 AC: 504949 AN: 1461080 Hom.: 88931 Cov.: 44 AF XY: 0.344 AC XY: 250034 AN XY: 726930

African (AFR) AF: 0.221 AC: 7412 AN: 33472

American (AMR) AF: 0.354 AC: 15816 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 9324 AN: 26132

East Asian (EAS) AF: 0.197 AC: 7809 AN: 39700

South Asian (SAS) AF: 0.272 AC: 23456 AN: 86246

European-Finnish (FIN) AF: 0.365 AC: 19485 AN: 53338

Middle Eastern (MID) AF: 0.375 AC: 2165 AN: 5768

European-Non Finnish (NFE) AF: 0.360 AC: 399585 AN: 1111358

Other (OTH) AF: 0.330 AC: 19897 AN: 60360

GnomAD4 genome AF: 0.311 AC: 47264 AN: 152028 Hom.: 7692 Cov.: 32 AF XY: 0.313 AC XY: 23263 AN XY: 74314

African (AFR) AF: 0.225 AC: 9316 AN: 41476

American (AMR) AF: 0.330 AC: 5029 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1264 AN: 3470

East Asian (EAS) AF: 0.177 AC: 915 AN: 5180

South Asian (SAS) AF: 0.260 AC: 1253 AN: 4810

European-Finnish (FIN) AF: 0.371 AC: 3916 AN: 10556

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.361 AC: 24519 AN: 67956

Other (OTH) AF: 0.319 AC: 674 AN: 2116

Alfa AF: 0.349 Hom.: 3224

Bravo AF: 0.301

Asia WGS AF: 0.207 AC: 719 AN: 3478

EpiCase AF: 0.357

EpiControl AF: 0.363

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.18
DANN	Benign	0.36
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.94	T
PhyloP100		-0.70
PrimateAI	Benign	0.16	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.0020
Sift	Benign	0.47	T
Sift4G	Benign	0.37	T
gMVP		0.013
Mutation Taster		=94/6	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2228212;

hg19: chr6-12124587;

COSMIC: COSV65098809;

COSMIC: COSV65098809;