rs213274

Variant names:

• chr7-18466964-C-A
• rs213274
• NM_001321868.2:c.26-29298C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-18466964-C-A
• chr7-18466964-C-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.26-29298C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.963 in 152,230 control chromosomes in the GnomAD database, including 70,666 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 (70666 hom., cov: 30)
• Consequence: HDAC9 NM_001321868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC9	NM_001321868.2	c.26-29298C>A		intron_variant	Intron 2 of 25		NP_001308797.1
HDAC9	NM_001321869.2	c.26-29298C>A		intron_variant	Intron 2 of 12		NP_001308798.1
HDAC9	NM_001321870.2	c.26-29298C>A		intron_variant	Intron 2 of 12		NP_001308799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000417496.6	c.85+8063C>A		intron_variant	Intron 3 of 12	2		ENSP00000401669.2
HDAC9	ENST00000707077.1	c.26-29298C>A		intron_variant	Intron 2 of 11			ENSP00000516728.1
HDAC9	ENST00000413509.6	c.-41-29298C>A		intron_variant	Intron 1 of 3	5		ENSP00000412497.2

Frequencies

GnomAD3 genomes AF: 0.963 AC: 146530 AN: 152112 Hom.: 70603 Cov.: 30

Gnomad AFR AF: 0.990

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.980

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.939

Gnomad FIN AF: 0.979

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.942

Gnomad OTH AF: 0.961

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

GnomAD4 genome AF: 0.963 AC: 146652 AN: 152230 Hom.: 70666 Cov.: 30 AF XY: 0.964 AC XY: 71763 AN XY: 74408

African (AFR) AF: 0.990 AC: 41126 AN: 41542

American (AMR) AF: 0.965 AC: 14750 AN: 15282

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

East Asian (EAS) AF: 1.00 AC: 5172 AN: 5174

South Asian (SAS) AF: 0.939 AC: 4526 AN: 4820

European-Finnish (FIN) AF: 0.979 AC: 10385 AN: 10608

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.942 AC: 64097 AN: 68018

Other (OTH) AF: 0.962 AC: 2030 AN: 2110

Alfa AF: 0.957 Hom.: 3787

Bravo AF: 0.963

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.48
DANN	Benign	0.12
PhyloP100		0.074
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: rs213274; hg19: chr7-18506587;