NM_006734.4:c.-527-11008A>G

Variant names:

• chr6-142794623-T-C
• rs533173
• NM_006734.4:c.-527-11008A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006734.4(HIVEP2):​c.-527-11008A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 152,082 control chromosomes in the GnomAD database, including 27,024 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 0.58 (27024 hom., cov: 32)
• Consequence: HIVEP2 NM_006734.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.973
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIVEP2	NM_006734.4	c.-527-11008A>G		intron_variant	Intron 2 of 9	ENST00000367603.8	NP_006725.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIVEP2	ENST00000367603.8	c.-527-11008A>G		intron_variant	Intron 2 of 9	1	NM_006734.4	ENSP00000356575.2

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88285 AN: 151966 Hom.: 27007 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.581 AC: 88345 AN: 152082 Hom.: 27024 Cov.: 32 AF XY: 0.583 AC XY: 43341 AN XY: 74328

African (AFR) AF: 0.397 AC: 16471 AN: 41476

American (AMR) AF: 0.505 AC: 7721 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2243 AN: 3472

East Asian (EAS) AF: 0.584 AC: 3017 AN: 5162

South Asian (SAS) AF: 0.652 AC: 3149 AN: 4828

European-Finnish (FIN) AF: 0.724 AC: 7648 AN: 10560

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46115 AN: 67980

Other (OTH) AF: 0.582 AC: 1230 AN: 2112

Alfa AF: 0.606 Hom.: 4697

Bravo AF: 0.556

Asia WGS AF: 0.625 AC: 2175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Benign	0.85
PhyloP100		0.97
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: rs533173; hg19: chr6-143115760; COSMIC: COSV50007581; COSMIC: COSV50007581;