rs2389963

Variant names:

• chr7-18548822-G-A
• rs2389963
• NM_178425.4:c.23-36459G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-18548822-G-A
• chr7-18548822-G-C
• chr7-18548822-G-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.23-36459G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 152,184 control chromosomes in the GnomAD database, including 44,580 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 0.76 (44580 hom., cov: 33)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.420
• 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

ENSG00000308101 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178425.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	NM_178425.4	MANE Select	c.23-36459G>A		intron	N/A	NP_848512.1	Q9UKV0-7
	HDAC9	NM_178423.3		c.23-36459G>A		intron	N/A	NP_848510.1	Q9UKV0-5
	HDAC9	NM_001321868.2		c.89-36459G>A		intron	N/A	NP_001308797.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	ENST00000686413.1	MANE Select	c.23-36459G>A		intron	N/A	ENSP00000509161.1	Q9UKV0-7
	HDAC9	ENST00000441542.7	TSL:1	c.23-36459G>A		intron	N/A	ENSP00000408617.2	Q9UKV0-7
	HDAC9	ENST00000406451.8	TSL:1	c.23-36459G>A		intron	N/A	ENSP00000384657.3	Q9UKV0-5

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114949 AN: 152064 Hom.: 44522 Cov.: 33

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.761

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.756 AC: 115067 AN: 152184 Hom.: 44580 Cov.: 33 AF XY: 0.751 AC XY: 55860 AN XY: 74392

African (AFR) AF: 0.937 AC: 38941 AN: 41552

American (AMR) AF: 0.721 AC: 11032 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2025 AN: 3466

East Asian (EAS) AF: 0.749 AC: 3871 AN: 5170

South Asian (SAS) AF: 0.738 AC: 3558 AN: 4818

European-Finnish (FIN) AF: 0.667 AC: 7051 AN: 10572

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46277 AN: 67998

Other (OTH) AF: 0.743 AC: 1567 AN: 2110

Alfa AF: 0.713 Hom.: 90016

Bravo AF: 0.770

Asia WGS AF: 0.764 AC: 2660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.61
PhyloP100		0.42
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: rs2389963; hg19: chr7-18588445;