chr7-18471372-C-T

Variant names:

• chr7-18471372-C-T
• rs213276
• NM_001321868.2:c.26-24890C>T

Variant summary

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

The NM_001321868.2(HDAC9):​c.26-24890C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.964 in 152,320 control chromosomes in the GnomAD database, including 70,860 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 0.96 (70860 hom., cov: 32)
• Consequence: HDAC9 NM_001321868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.982 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.26-24890C>T		intron	N/A	NP_001308797.1
	HDAC9	NM_001321869.2		c.26-24890C>T		intron	N/A	NP_001308798.1
	HDAC9	NM_001321870.2		c.26-24890C>T		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.85+12471C>T		intron	N/A	ENSP00000401669.2
	HDAC9	ENST00000707077.1		c.26-24890C>T		intron	N/A	ENSP00000516728.1
	HDAC9	ENST00000413509.6	TSL:5	c.-41-24890C>T		intron	N/A	ENSP00000412497.2

Frequencies

GnomAD3 genomes AF: 0.964 AC: 146780 AN: 152202 Hom.: 70797 Cov.: 32

Gnomad AFR AF: 0.990

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.966

Gnomad ASJ AF: 0.980

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.939

Gnomad FIN AF: 0.980

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.944

Gnomad OTH AF: 0.961

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

GnomAD4 genome AF: 0.964 AC: 146903 AN: 152320 Hom.: 70860 Cov.: 32 AF XY: 0.965 AC XY: 71917 AN XY: 74490

African (AFR) AF: 0.990 AC: 41164 AN: 41570

American (AMR) AF: 0.966 AC: 14769 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.980 AC: 3399 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5186

South Asian (SAS) AF: 0.939 AC: 4530 AN: 4822

European-Finnish (FIN) AF: 0.980 AC: 10410 AN: 10626

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.944 AC: 64232 AN: 68038

Other (OTH) AF: 0.962 AC: 2033 AN: 2114

Alfa AF: 0.949 Hom.: 55125

Bravo AF: 0.964

Asia WGS AF: 0.975 AC: 3390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.70
DANN	Benign	0.54
PhyloP100		-0.15
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: rs213276; hg19: chr7-18510995;