rs2389995

Variant names:

• chr7-18933395-A-G
• rs2389995
• NM_178425.4:c.2804-2414A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-18933395-A-G
• chr7-18933395-A-T

Variant summary

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

The NM_178425.4(HDAC9):​c.2804-2414A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0609 in 152,100 control chromosomes in the GnomAD database, including 622 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 0.061 (622 hom., cov: 31)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC9	NM_178425.4	c.2804-2414A>G		intron_variant	Intron 22 of 25	ENST00000686413.1	NP_848512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000686413.1	c.2804-2414A>G		intron_variant	Intron 22 of 25		NM_178425.4	ENSP00000509161.1

Frequencies

GnomAD3 genomes AF: 0.0608 AC: 9243 AN: 151982 Hom.: 622 Cov.: 31

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.0366

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00268

Gnomad OTH AF: 0.0492

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

GnomAD4 genome AF: 0.0609 AC: 9259 AN: 152100 Hom.: 622 Cov.: 31 AF XY: 0.0619 AC XY: 4603 AN XY: 74360

African (AFR) AF: 0.144 AC: 5987 AN: 41470

American (AMR) AF: 0.103 AC: 1569 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3470

East Asian (EAS) AF: 0.205 AC: 1055 AN: 5140

South Asian (SAS) AF: 0.0367 AC: 177 AN: 4828

European-Finnish (FIN) AF: 0.0101 AC: 107 AN: 10610

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00268 AC: 182 AN: 67986

Other (OTH) AF: 0.0506 AC: 107 AN: 2114

Alfa AF: 0.0245 Hom.: 384

Bravo AF: 0.0769

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.8
DANN	Benign	0.57
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2389995; hg19: chr7-18973018;