rs12211360

Variant names:

• chr6-142798695-A-G
• rs12211360
• NM_006734.4:c.-527-15080T>C

Variant summary

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

The NM_006734.4(HIVEP2):​c.-527-15080T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,186 control chromosomes in the GnomAD database, including 1,376 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 0.12 (1376 hom., cov: 32)
• Consequence: HIVEP2 NM_006734.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIVEP2	NM_006734.4	c.-527-15080T>C		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.-527-15080T>C		intron_variant	Intron 2 of 9	1	NM_006734.4	ENSP00000356575.2

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18120 AN: 152066 Hom.: 1378 Cov.: 32

Gnomad AFR AF: 0.0313

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0305

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.119 AC: 18101 AN: 152186 Hom.: 1376 Cov.: 32 AF XY: 0.118 AC XY: 8759 AN XY: 74394

African (AFR) AF: 0.0311 AC: 1294 AN: 41556

American (AMR) AF: 0.127 AC: 1935 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 524 AN: 3470

East Asian (EAS) AF: 0.0306 AC: 158 AN: 5160

South Asian (SAS) AF: 0.160 AC: 769 AN: 4818

European-Finnish (FIN) AF: 0.135 AC: 1430 AN: 10590

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11496 AN: 68000

Other (OTH) AF: 0.137 AC: 289 AN: 2114

Alfa AF: 0.144 Hom.: 641

Bravo AF: 0.112

Asia WGS AF: 0.0970 AC: 337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.1
DANN	Benign	0.42
PhyloP100		1.7
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: rs12211360; hg19: chr6-143119832;