7-18370158-T-C

Variant names:

• chr7-18370158-T-C
• rs10486301
• NM_001321868.2:c.26-126104T>C

Variant summary

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

The NM_001321868.2(HDAC9):​c.26-126104T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,100 control chromosomes in the GnomAD database, including 2,879 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 0.18 (2879 hom., cov: 32)
• Consequence: HDAC9 NM_001321868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.569
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321868.2. 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_001321868.2		c.26-126104T>C		intron	N/A	NP_001308797.1
	HDAC9	NM_001321869.2		c.26-126104T>C		intron	N/A	NP_001308798.1
	HDAC9	NM_001321870.2		c.26-126104T>C		intron	N/A	NP_001308799.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	ENST00000417496.6	TSL:2	c.26-88684T>C		intron	N/A	ENSP00000401669.2
	HDAC9	ENST00000707077.1		c.26-126104T>C		intron	N/A	ENSP00000516728.1
	HDAC9	ENST00000413509.6	TSL:5	c.-42+79643T>C		intron	N/A	ENSP00000412497.2

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26965 AN: 151982 Hom.: 2878 Cov.: 32

Gnomad AFR AF: 0.0673

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.177 AC: 26967 AN: 152100 Hom.: 2879 Cov.: 32 AF XY: 0.177 AC XY: 13183 AN XY: 74350

African (AFR) AF: 0.0671 AC: 2786 AN: 41506

American (AMR) AF: 0.220 AC: 3351 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3470

East Asian (EAS) AF: 0.216 AC: 1118 AN: 5174

South Asian (SAS) AF: 0.145 AC: 700 AN: 4826

European-Finnish (FIN) AF: 0.253 AC: 2679 AN: 10584

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15124 AN: 67964

Other (OTH) AF: 0.179 AC: 377 AN: 2112

Alfa AF: 0.108 Hom.: 225

Bravo AF: 0.170

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.8
DANN	Benign	0.55
PhyloP100		0.57
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10486301; hg19: chr7-18409781;