rs10243618

Variant names:

• chr7-18483117-G-A
• rs10243618
• NM_001321868.2:c.26-13145G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-18483117-G-A
• chr7-18483117-G-C

Variant summary

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

The NM_001321868.2(HDAC9):​c.26-13145G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 151,900 control chromosomes in the GnomAD database, including 9,686 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 0.34 (9686 hom., cov: 32)
• Consequence: HDAC9 NM_001321868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• 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

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 (AFR) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321868.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	NM_001321868.2		c.26-13145G>A		intron	N/A	NP_001308797.1
	HDAC9	NM_001321869.2		c.26-13145G>A		intron	N/A	NP_001308798.1
	HDAC9	NM_001321870.2		c.26-13145G>A		intron	N/A	NP_001308799.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	ENST00000417496.6	TSL:2	c.86-13145G>A		intron	N/A	ENSP00000401669.2
	HDAC9	ENST00000707077.1		c.26-13145G>A		intron	N/A	ENSP00000516728.1
	HDAC9	ENST00000413509.6	TSL:5	c.-41-13145G>A		intron	N/A	ENSP00000412497.2

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51264 AN: 151780 Hom.: 9637 Cov.: 32

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.338 AC: 51368 AN: 151900 Hom.: 9686 Cov.: 32 AF XY: 0.341 AC XY: 25296 AN XY: 74252

African (AFR) AF: 0.506 AC: 20905 AN: 41352

American (AMR) AF: 0.267 AC: 4077 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1231 AN: 3468

East Asian (EAS) AF: 0.341 AC: 1763 AN: 5170

South Asian (SAS) AF: 0.318 AC: 1534 AN: 4822

European-Finnish (FIN) AF: 0.268 AC: 2829 AN: 10544

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17907 AN: 67958

Other (OTH) AF: 0.340 AC: 718 AN: 2110

Alfa AF: 0.286 Hom.: 10578

Bravo AF: 0.342

Asia WGS AF: 0.346 AC: 1202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.88
DANN	Benign	0.14
PhyloP100		0.086
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10243618; hg19: chr7-18522740;