rs186172414

Variant names:

• chrX-72351602-G-A
• rs186172414
• NM_018486.3:c.1111+131C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-72351602-G-A
• chrX-72351602-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_018486.3(HDAC8):​c.1111+131C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 468,552 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. 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 0.000053 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.000014 (0 hom. 0 hem.)
• Consequence: HDAC8 NM_018486.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.52
• Publications: 0 publications found

Genes affected

HDAC8 (HGNC:13315): (histone deacetylase 8) Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class I of the histone deacetylase family. It catalyzes the deacetylation of lysine residues in the histone N-terminal tails and represses transcription in large multiprotein complexes with transcriptional co-repressors. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

HDAC8 Gene-Disease associations (from GenCC):

• Cornelia de Lange syndrome

  Inheritance: XL, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Cornelia de Lange syndrome 5

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Wilson-Turner syndrome

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285547 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0000534 (6/112279) while in subpopulation AFR AF = 0.000194 (6/30904). AF 95% confidence interval is 0.0000845. There are 0 homozygotes in GnomAd4. There are 2 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High AC in GnomAd4 at 6 XL,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018486.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC8	NM_018486.3	MANE Select	c.1111+131C>T		intron	N/A	NP_060956.1	Q9BY41-1
	HDAC8	NM_001410725.1		c.1111+131C>T		intron	N/A	NP_001397654.1	A0A3B3IS68
	HDAC8	NM_001410727.1		c.1033+131C>T		intron	N/A	NP_001397656.1	A6NFW1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC8	ENST00000373573.9	TSL:1 MANE Select	c.1111+131C>T		intron	N/A	ENSP00000362674.3	Q9BY41-1
	ENSG00000285547	ENST00000648922.1		c.1111+131C>T		intron	N/A	ENSP00000497072.1	A0A3B3IRV1
	HDAC8	ENST00000373568.7	TSL:5	c.1242C>T	p.Leu414Leu	synonymous	Exon 10 of 10	ENSP00000362669.3	A6NGJ7

Frequencies

GnomAD3 genomes AF: 0.0000534 AC: 6 AN: 112279 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000140 AC: 5 AN: 356273 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 117741

African (AFR) AF: 0.000195 AC: 2 AN: 10265

American (AMR) AF: 0.000122 AC: 2 AN: 16360

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10476

East Asian (EAS) AF: 0.00 AC: 0 AN: 23397

South Asian (SAS) AF: 0.00 AC: 0 AN: 27410

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1476

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 214899

Other (OTH) AF: 0.0000486 AC: 1 AN: 20572

GnomAD4 genome AF: 0.0000534 AC: 6 AN: 112279 Hom.: 0 Cov.: 23 AF XY: 0.0000581 AC XY: 2 AN XY: 34427

African (AFR) AF: 0.000194 AC: 6 AN: 30904

American (AMR) AF: 0.00 AC: 0 AN: 10662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3575

South Asian (SAS) AF: 0.00 AC: 0 AN: 2707

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6125

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53222

Other (OTH) AF: 0.00 AC: 0 AN: 1511

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.59
PhyloP100		2.5

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: rs186172414; hg19: chrX-71571452;