rs11505418

Variant names:

• chr7-18953626-T-C
• rs11505418
• NM_178425.4:c.2938-520T>C

Variant summary

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

The NM_178425.4(HDAC9):​c.2938-520T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,048 control chromosomes in the GnomAD database, including 10,885 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 0.36 (10885 hom., cov: 33)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• Publications: 6 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 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.2938-520T>C		intron	N/A	NP_848512.1	Q9UKV0-7
	HDAC9	NM_178423.3		c.2929-520T>C		intron	N/A	NP_848510.1	Q9UKV0-5
	HDAC9	NM_001321868.2		c.2863-520T>C		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.2938-520T>C		intron	N/A	ENSP00000509161.1	Q9UKV0-7
	HDAC9	ENST00000441542.7	TSL:1	c.2938-520T>C		intron	N/A	ENSP00000408617.2	Q9UKV0-7
	HDAC9	ENST00000406451.8	TSL:1	c.2929-520T>C		intron	N/A	ENSP00000384657.3	Q9UKV0-5

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55106 AN: 151930 Hom.: 10890 Cov.: 33

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.362 AC: 55105 AN: 152048 Hom.: 10885 Cov.: 33 AF XY: 0.359 AC XY: 26708 AN XY: 74308

African (AFR) AF: 0.213 AC: 8866 AN: 41532

American (AMR) AF: 0.355 AC: 5411 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1381 AN: 3470

East Asian (EAS) AF: 0.261 AC: 1348 AN: 5166

South Asian (SAS) AF: 0.307 AC: 1480 AN: 4818

European-Finnish (FIN) AF: 0.395 AC: 4170 AN: 10562

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31198 AN: 67944

Other (OTH) AF: 0.378 AC: 799 AN: 2114

Alfa AF: 0.424 Hom.: 57545

Bravo AF: 0.354

Asia WGS AF: 0.299 AC: 1038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.8
DANN	Benign	0.75
PhyloP100		1.4
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: rs11505418; hg19: chr7-18993249; COSMIC: COSV67783936; COSMIC: COSV67783936;