7-18706590-A-G

Variant names:

• chr7-18706590-A-G
• rs1178112
• NM_178425.4:c.1732-20990A>G

Variant summary

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

The NM_178425.4(HDAC9):​c.1732-20990A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,274 control chromosomes in the GnomAD database, including 2,206 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 0.15 (2206 hom., cov: 32)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC9	NM_178425.4	c.1732-20990A>G		intron_variant	Intron 12 of 25	ENST00000686413.1	NP_848512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000686413.1	c.1732-20990A>G		intron_variant	Intron 12 of 25		NM_178425.4	ENSP00000509161.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23243 AN: 152156 Hom.: 2203 Cov.: 32

Gnomad AFR AF: 0.0391

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.153 AC: 23243 AN: 152274 Hom.: 2206 Cov.: 32 AF XY: 0.154 AC XY: 11462 AN XY: 74442

African (AFR) AF: 0.0391 AC: 1625 AN: 41582

American (AMR) AF: 0.216 AC: 3304 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 738 AN: 3468

East Asian (EAS) AF: 0.274 AC: 1416 AN: 5174

South Asian (SAS) AF: 0.245 AC: 1182 AN: 4826

European-Finnish (FIN) AF: 0.156 AC: 1650 AN: 10604

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12829 AN: 68014

Other (OTH) AF: 0.159 AC: 335 AN: 2112

Alfa AF: 0.0751 Hom.: 119

Bravo AF: 0.150

Asia WGS AF: 0.242 AC: 838 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.56
PhyloP100		0.19
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: rs1178112; hg19: chr7-18746213;