rs10486302

Variant names:

• chr7-18369244-C-G
• rs10486302
• NM_001321868.2:c.26-127018C>G

Variant summary

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

The NM_001321868.2(HDAC9):​c.26-127018C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0517 in 152,002 control chromosomes in the GnomAD database, including 352 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 0.052 (352 hom., cov: 32)
• Consequence: HDAC9 NM_001321868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.894
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 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.26-127018C>G		intron	N/A	NP_001308797.1
	HDAC9	NM_001321869.2		c.26-127018C>G		intron	N/A	NP_001308798.1
	HDAC9	NM_001321870.2		c.26-127018C>G		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.26-89598C>G		intron	N/A	ENSP00000401669.2
	HDAC9	ENST00000707077.1		c.26-127018C>G		intron	N/A	ENSP00000516728.1
	HDAC9	ENST00000413509.6	TSL:5	c.-42+78729C>G		intron	N/A	ENSP00000412497.2

Frequencies

GnomAD3 genomes AF: 0.0514 AC: 7807 AN: 151884 Hom.: 342 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0287

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.0897

Gnomad SAS AF: 0.0323

Gnomad FIN AF: 0.0165

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.0407

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

GnomAD4 genome AF: 0.0517 AC: 7853 AN: 152002 Hom.: 352 Cov.: 32 AF XY: 0.0516 AC XY: 3834 AN XY: 74308

African (AFR) AF: 0.120 AC: 4961 AN: 41458

American (AMR) AF: 0.0287 AC: 438 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 57 AN: 3468

East Asian (EAS) AF: 0.0896 AC: 463 AN: 5170

South Asian (SAS) AF: 0.0325 AC: 157 AN: 4826

European-Finnish (FIN) AF: 0.0165 AC: 174 AN: 10574

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0220 AC: 1492 AN: 67946

Other (OTH) AF: 0.0403 AC: 85 AN: 2110

Alfa AF: 0.0399 Hom.: 23

Bravo AF: 0.0558

Asia WGS AF: 0.0540 AC: 186 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.30
DANN	Benign	0.66
PhyloP100		-0.89
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: rs10486302; hg19: chr7-18408867;