rs1178118

Positions:

• chr7-18712375-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDAC9	NM_178425.4	c.1732-15205T>C		intron_variant		ENST00000686413.1	NP_848512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000686413.1	c.1732-15205T>C		intron_variant			NM_178425.4	ENSP00000509161	P4

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

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.202

Alfa AF: 0.197 Hom.: 6173

Bravo AF: 0.225

Asia WGS AF: 0.283 AC: 982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.69
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs1178118; hg19: chr7-18751998;