dbSNP rs10486295: HDAC9:c.26-89078G>A (chr7-18407184-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001321868.2(HDAC9):c.26-89078G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0617 in 152,050 control chromosomes in the GnomAD database, including 610 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 0.062 ( 610 hom., cov: 32)

Consequence

HDAC9
NM_001321868.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.409

Publications

1 publications found

Variant links:

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

HDAC9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
HDAC9	NM_001321868.2 link	c.26-89078G>A	intron_variant	Intron 2 of 25	NP_001308797.1	Q9UKV0
HDAC9	NM_001321869.2 link	c.26-89078G>A	intron_variant	Intron 2 of 12	NP_001308798.1	Q9UKV0B7Z3P7
HDAC9	NM_001321870.2 link	c.26-89078G>A	intron_variant	Intron 2 of 12	NP_001308799.1	Q9UKV0B7Z3P7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
HDAC9	ENST00000417496.6 link	c.26-51658G>A	intron_variant	Intron 2 of 12	2	ENSP00000401669.2	Q9UKV0-8
HDAC9	ENST00000707077.1 link	c.26-89078G>A	intron_variant	Intron 2 of 11		ENSP00000516728.1	A0A9L9PXL9
HDAC9	ENST00000413509.6 link	c.-41-89078G>A	intron_variant	Intron 1 of 3	5	ENSP00000412497.2	C9IZS0

Frequencies

GnomAD3 genomes

AF:

0.0615

AC:

9351

AN:

151932

Hom.:

604

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0454

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.177

Gnomad SAS

AF:

0.0886

Gnomad FIN

AF:

0.00312

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0113

Gnomad OTH

AF:

0.0541

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

GnomAD4 genome

AF:

0.0617

AC:

9381

AN:

152050

Hom.:

610

Cov.:

AF XY:

0.0631

AC XY:

4694

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.154

AC:

6377

AN:

41454

American (AMR)

AF:

0.0454

AC:

693

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0101

AC:

AN:

3470

East Asian (EAS)

AF:

0.178

AC:

916

AN:

5160

South Asian (SAS)

AF:

0.0895

AC:

431

AN:

4816

European-Finnish (FIN)

AF:

0.00312

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0113

AC:

767

AN:

67978

Other (OTH)

AF:

0.0545

AC:

115

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

418

836

1253

1671

2089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0424

Hom.:

Bravo

AF:

0.0674

Asia WGS

AF:

0.128

AC:

444

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.69

(source)

DANN

Benign

0.64

PhyloP100

-0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over