chr6-142753563-T-C

Variant names:

• chr6-142753563-T-C
• rs169098
• NM_006734.4:c.6885A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006734.4(HIVEP2):​c.6885A>G​(p.Pro2295Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 1,613,816 control chromosomes in the GnomAD database, including 355,760 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38756 hom., cov: 32)
  • Exomes 𝑓: 0.66 (317004 hom.)
• Consequence: HIVEP2 NM_006734.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.141
• Publications: 18 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

ENSG00000233138 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-142753563-T-C is Benign according to our data. Variant chr6-142753563-T-C is described in ClinVar as Benign. ClinVar VariationId is 402939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.141 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.831 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.6885A>G	p.Pro2295Pro	synonymous	Exon 10 of 10	NP_006725.3
	HIVEP2	NM_001438449.1		c.6885A>G	p.Pro2295Pro	synonymous	Exon 10 of 10	NP_001425378.1
	HIVEP2	NM_001438450.1		c.6885A>G	p.Pro2295Pro	synonymous	Exon 11 of 11	NP_001425379.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIVEP2	ENST00000367603.8	TSL:1 MANE Select	c.6885A>G	p.Pro2295Pro	synonymous	Exon 10 of 10	ENSP00000356575.2
	HIVEP2	ENST00000012134.7	TSL:5	c.6885A>G	p.Pro2295Pro	synonymous	Exon 9 of 9	ENSP00000012134.2
	HIVEP2	ENST00000367604.6	TSL:5	c.6885A>G	p.Pro2295Pro	synonymous	Exon 10 of 10	ENSP00000356576.1

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107554 AN: 151974 Hom.: 38716 Cov.: 32

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.703

GnomAD2 exomes AF: 0.686 AC: 170775 AN: 249086 AF XY: 0.684

Gnomad AFR exome AF: 0.841

Gnomad AMR exome AF: 0.679

Gnomad ASJ exome AF: 0.696

Gnomad EAS exome AF: 0.841

Gnomad FIN exome AF: 0.640

Gnomad NFE exome AF: 0.633

Gnomad OTH exome AF: 0.652

GnomAD4 exome AF: 0.656 AC: 959160 AN: 1461724 Hom.: 317004 Cov.: 57 AF XY: 0.659 AC XY: 478866 AN XY: 727178

African (AFR) AF: 0.848 AC: 28387 AN: 33480

American (AMR) AF: 0.681 AC: 30474 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 18286 AN: 26136

East Asian (EAS) AF: 0.836 AC: 33209 AN: 39700

South Asian (SAS) AF: 0.754 AC: 65027 AN: 86256

European-Finnish (FIN) AF: 0.634 AC: 33850 AN: 53382

Middle Eastern (MID) AF: 0.714 AC: 4119 AN: 5768

European-Non Finnish (NFE) AF: 0.634 AC: 705016 AN: 1111886

Other (OTH) AF: 0.675 AC: 40792 AN: 60392

GnomAD4 genome AF: 0.708 AC: 107647 AN: 152092 Hom.: 38756 Cov.: 32 AF XY: 0.708 AC XY: 52630 AN XY: 74332

African (AFR) AF: 0.838 AC: 34804 AN: 41534

American (AMR) AF: 0.669 AC: 10209 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 2439 AN: 3472

East Asian (EAS) AF: 0.831 AC: 4291 AN: 5162

South Asian (SAS) AF: 0.757 AC: 3650 AN: 4824

European-Finnish (FIN) AF: 0.648 AC: 6841 AN: 10554

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.633 AC: 42996 AN: 67964

Other (OTH) AF: 0.704 AC: 1486 AN: 2110

Alfa AF: 0.659 Hom.: 137256

Bravo AF: 0.714

Asia WGS AF: 0.773 AC: 2688 AN: 3478

EpiCase AF: 0.636

EpiControl AF: 0.628

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Intellectual disability, autosomal dominant 43 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.61
DANN	Benign	0.37
PhyloP100		-0.14
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: rs169098; hg19: chr6-143074700; COSMIC: COSV50005685;