7-18352248-C-T

Variant names:

• chr7-18352248-C-T
• rs615545
• NM_001321868.2:c.26-144014C>T

Variant summary

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

The NM_001321868.2(HDAC9):​c.26-144014C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 151,874 control chromosomes in the GnomAD database, including 9,316 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 (9316 hom., cov: 32)
• Consequence: HDAC9 NM_001321868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.456
• 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=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC9	NM_001321868.2	c.26-144014C>T		intron_variant	Intron 2 of 25		NP_001308797.1
HDAC9	NM_001321869.2	c.26-144014C>T		intron_variant	Intron 2 of 12		NP_001308798.1
HDAC9	NM_001321870.2	c.26-144014C>T		intron_variant	Intron 2 of 12		NP_001308799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000417496.6	c.26-106594C>T		intron_variant	Intron 2 of 12	2		ENSP00000401669.2
HDAC9	ENST00000707077.1	c.26-144014C>T		intron_variant	Intron 2 of 11			ENSP00000516728.1
HDAC9	ENST00000413509.6	c.-42+61733C>T		intron_variant	Intron 1 of 3	5		ENSP00000412497.2

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51788 AN: 151754 Hom.: 9304 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.341 AC: 51841 AN: 151874 Hom.: 9316 Cov.: 32 AF XY: 0.342 AC XY: 25416 AN XY: 74222

African (AFR) AF: 0.446 AC: 18457 AN: 41402

American (AMR) AF: 0.287 AC: 4383 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1132 AN: 3466

East Asian (EAS) AF: 0.449 AC: 2307 AN: 5142

South Asian (SAS) AF: 0.393 AC: 1891 AN: 4816

European-Finnish (FIN) AF: 0.279 AC: 2947 AN: 10554

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19728 AN: 67936

Other (OTH) AF: 0.320 AC: 675 AN: 2108

Alfa AF: 0.302 Hom.: 4199

Bravo AF: 0.347

Asia WGS AF: 0.425 AC: 1472 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		0.46
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: rs615545; hg19: chr7-18391871;