rs12205474

Variant names:

• chr6-142778142-G-C
• rs12205474
• NM_006734.4:c.-432-1951C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006734.4(HIVEP2):​c.-432-1951C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,210 control chromosomes in the GnomAD database, including 1,993 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (1993 hom., cov: 32)
• Consequence: HIVEP2 NM_006734.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.606
• Publications: 2 publications found

Genes affected

HIVEP2 (HGNC:4921): (HIVEP zinc finger 2) This gene encodes a member of a family of closely related, large, zinc finger-containing transcription factors. The encoded protein regulates transcription by binding to regulatory regions of various cellular and viral genes that maybe involved in growth, development and metastasis. The protein contains the ZAS domain comprised of two widely separated regions of zinc finger motifs, a stretch of highly acidic amino acids and a serine/threonine-rich sequence. [provided by RefSeq, Nov 2012]

HIVEP2 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 43

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006734.4. 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
	HIVEP2	NM_006734.4	MANE Select	c.-432-1951C>G		intron	N/A	NP_006725.3
	HIVEP2	NM_001438449.1		c.-432-1951C>G		intron	N/A	NP_001425378.1
	HIVEP2	NM_001438450.1		c.-432-1951C>G		intron	N/A	NP_001425379.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIVEP2	ENST00000367603.8	TSL:1 MANE Select	c.-432-1951C>G		intron	N/A	ENSP00000356575.2
	HIVEP2	ENST00000012134.7	TSL:5	c.-432-1951C>G		intron	N/A	ENSP00000012134.2
	HIVEP2	ENST00000367604.6	TSL:5	c.-432-1951C>G		intron	N/A	ENSP00000356576.1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23389 AN: 152092 Hom.: 1996 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.0743

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.172

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.154 AC: 23374 AN: 152210 Hom.: 1993 Cov.: 32 AF XY: 0.151 AC XY: 11247 AN XY: 74422

African (AFR) AF: 0.105 AC: 4354 AN: 41532

American (AMR) AF: 0.151 AC: 2313 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 616 AN: 3470

East Asian (EAS) AF: 0.0748 AC: 388 AN: 5186

South Asian (SAS) AF: 0.229 AC: 1108 AN: 4828

European-Finnish (FIN) AF: 0.119 AC: 1259 AN: 10576

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12745 AN: 68004

Other (OTH) AF: 0.170 AC: 360 AN: 2114

Alfa AF: 0.169 Hom.: 279

Bravo AF: 0.150

Asia WGS AF: 0.149 AC: 515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.30
DANN	Benign	0.61
PhyloP100		-0.61
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: rs12205474; hg19: chr6-143099279;