rs1178118

Variant names:

• chr7-18712375-T-C
• rs1178118
• NM_178425.4:c.1732-15205T>C

Variant summary

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

The NM_178425.4(HDAC9):​c.1732-15205T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,110 control chromosomes in the GnomAD database, including 3,818 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 0.22 (3818 hom., cov: 32)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 6 publications found

Genes affected

HDAC9 (HGNC:14065): (histone deacetylase 9) 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 has sequence homology to members of the histone deacetylase family. This gene is orthologous to the Xenopus and mouse MITR genes. The MITR protein lacks the histone deacetylase catalytic domain. It represses MEF2 activity through recruitment of multicomponent corepressor complexes that include CtBP and HDACs. This encoded protein may play a role in hematopoiesis. Multiple alternatively spliced transcripts have been described for this gene but the full-length nature of some of them has not been determined. [provided by RefSeq, Jul 2008]

HDAC9 Gene-Disease associations (from GenCC):

• auriculocondylar syndrome 4

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178425.4. 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
	HDAC9	NM_178425.4	MANE Select	c.1732-15205T>C		intron	N/A	NP_848512.1
	HDAC9	NM_178423.3		c.1723-15205T>C		intron	N/A	NP_848510.1
	HDAC9	NM_001321868.2		c.1657-15205T>C		intron	N/A	NP_001308797.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	ENST00000686413.1	MANE Select	c.1732-15205T>C		intron	N/A	ENSP00000509161.1
	HDAC9	ENST00000441542.7	TSL:1	c.1732-15205T>C		intron	N/A	ENSP00000408617.2
	HDAC9	ENST00000406451.8	TSL:1	c.1723-15205T>C		intron	N/A	ENSP00000384657.3

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33335 AN: 151992 Hom.: 3810 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.219 AC: 33366 AN: 152110 Hom.: 3818 Cov.: 32 AF XY: 0.220 AC XY: 16354 AN XY: 74368

African (AFR) AF: 0.272 AC: 11296 AN: 41484

American (AMR) AF: 0.230 AC: 3517 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3472

East Asian (EAS) AF: 0.305 AC: 1572 AN: 5162

South Asian (SAS) AF: 0.270 AC: 1302 AN: 4822

European-Finnish (FIN) AF: 0.157 AC: 1666 AN: 10594

Middle Eastern (MID) AF: 0.250 AC: 73 AN: 292

European-Non Finnish (NFE) AF: 0.186 AC: 12665 AN: 67980

Other (OTH) AF: 0.202 AC: 425 AN: 2108

Alfa AF: 0.203 Hom.: 13531

Bravo AF: 0.225

Asia WGS AF: 0.283 AC: 982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.69
DANN	Benign	0.51
PhyloP100		-1.4
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: rs1178118; hg19: chr7-18751998;