rs2520343

Variant names:

• chr7-18804185-C-A
• rs2520343
• NM_178425.4:c.2322+10733C>A

Variant summary

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

The NM_178425.4(HDAC9):​c.2322+10733C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,002 control chromosomes in the GnomAD database, including 14,580 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 0.41 (14580 hom., cov: 32)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC9	NM_178425.4	c.2322+10733C>A		intron_variant	Intron 17 of 25	ENST00000686413.1	NP_848512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000686413.1	c.2322+10733C>A		intron_variant	Intron 17 of 25		NM_178425.4	ENSP00000509161.1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61699 AN: 151884 Hom.: 14548 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.0923

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.406 AC: 61783 AN: 152002 Hom.: 14580 Cov.: 32 AF XY: 0.403 AC XY: 29918 AN XY: 74282

African (AFR) AF: 0.662 AC: 27458 AN: 41468

American (AMR) AF: 0.313 AC: 4781 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1477 AN: 3468

East Asian (EAS) AF: 0.0927 AC: 478 AN: 5154

South Asian (SAS) AF: 0.347 AC: 1673 AN: 4822

European-Finnish (FIN) AF: 0.352 AC: 3711 AN: 10540

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 20988 AN: 67968

Other (OTH) AF: 0.382 AC: 804 AN: 2106

Alfa AF: 0.339 Hom.: 5855

Bravo AF: 0.413

Asia WGS AF: 0.278 AC: 966 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.72
DANN	Benign	0.34
PhyloP100		-0.14
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: rs2520343; hg19: chr7-18843808;