rs197508

Variant names:

• chr6-142776356-G-A
• rs197508
• NM_006734.4:c.-432-165C>T

Variant summary

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

The NM_006734.4(HIVEP2):​c.-432-165C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 151,986 control chromosomes in the GnomAD database, including 25,327 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 0.57 (25327 hom., cov: 32)
• Consequence: HIVEP2 NM_006734.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIVEP2	NM_006734.4	c.-432-165C>T		intron_variant	Intron 3 of 9	ENST00000367603.8	NP_006725.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIVEP2	ENST00000367603.8	c.-432-165C>T		intron_variant	Intron 3 of 9	1	NM_006734.4	ENSP00000356575.2

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87210 AN: 151868 Hom.: 25310 Cov.: 32

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.574 AC: 87279 AN: 151986 Hom.: 25327 Cov.: 32 AF XY: 0.576 AC XY: 42757 AN XY: 74268

African (AFR) AF: 0.557 AC: 23057 AN: 41418

American (AMR) AF: 0.475 AC: 7252 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1865 AN: 3468

East Asian (EAS) AF: 0.548 AC: 2834 AN: 5176

South Asian (SAS) AF: 0.569 AC: 2742 AN: 4820

European-Finnish (FIN) AF: 0.657 AC: 6937 AN: 10556

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.600 AC: 40756 AN: 67964

Other (OTH) AF: 0.560 AC: 1180 AN: 2108

Alfa AF: 0.587 Hom.: 81930

Bravo AF: 0.562

Asia WGS AF: 0.572 AC: 1993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.68
DANN	Benign	0.47
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs197508; hg19: chr6-143097493; COSMIC: COSV50007500; COSMIC: COSV50007500;