chr6-142820440-A-T

Variant names:

• chr6-142820440-A-T
• rs10484587
• NM_006734.4:c.-528+16495T>A

Variant summary

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

The NM_006734.4(HIVEP2):​c.-528+16495T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 151,970 control chromosomes in the GnomAD database, including 2,624 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 0.16 (2624 hom., cov: 31)
• Consequence: HIVEP2 NM_006734.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 1 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIVEP2	NM_006734.4	c.-528+16495T>A		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.-528+16495T>A		intron_variant	Intron 2 of 9	1	NM_006734.4	ENSP00000356575.2

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24755 AN: 151852 Hom.: 2628 Cov.: 31

Gnomad AFR AF: 0.0454

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.0426

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.163 AC: 24736 AN: 151970 Hom.: 2624 Cov.: 31 AF XY: 0.159 AC XY: 11798 AN XY: 74264

African (AFR) AF: 0.0452 AC: 1877 AN: 41492

American (AMR) AF: 0.173 AC: 2647 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 881 AN: 3466

East Asian (EAS) AF: 0.0427 AC: 221 AN: 5174

South Asian (SAS) AF: 0.218 AC: 1048 AN: 4812

European-Finnish (FIN) AF: 0.153 AC: 1616 AN: 10540

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15768 AN: 67912

Other (OTH) AF: 0.191 AC: 403 AN: 2108

Alfa AF: 0.201 Hom.: 438

Bravo AF: 0.155

Asia WGS AF: 0.140 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		1.1
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: rs10484587; hg19: chr6-143141577;