7-18721785-C-T

Variant names:

• chr7-18721785-C-T
• rs10225230
• NM_178425.4:c.1732-5795C>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.1732-5795C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.085 in 152,162 control chromosomes in the GnomAD database, including 1,111 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 0.085 (1111 hom., cov: 32)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 1 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 = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC9	NM_178425.4	c.1732-5795C>T		intron_variant	Intron 12 of 25	ENST00000686413.1	NP_848512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000686413.1	c.1732-5795C>T		intron_variant	Intron 12 of 25		NM_178425.4	ENSP00000509161.1

Frequencies

GnomAD3 genomes AF: 0.0847 AC: 12881 AN: 152046 Hom.: 1095 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0466

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0332

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0318

Gnomad OTH AF: 0.0746

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

GnomAD4 genome AF: 0.0850 AC: 12927 AN: 152162 Hom.: 1111 Cov.: 32 AF XY: 0.0830 AC XY: 6176 AN XY: 74394

African (AFR) AF: 0.223 AC: 9246 AN: 41482

American (AMR) AF: 0.0464 AC: 710 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3468

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0328 AC: 158 AN: 4820

European-Finnish (FIN) AF: 0.0386 AC: 409 AN: 10602

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0318 AC: 2165 AN: 68002

Other (OTH) AF: 0.0738 AC: 156 AN: 2114

Alfa AF: 0.0465 Hom.: 214

Bravo AF: 0.0916

Asia WGS AF: 0.0380 AC: 131 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	0.086
DANN	Benign	0.67
PhyloP100		-2.1
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: rs10225230; hg19: chr7-18761408;