NM_178425.4:c.2804-709T>G

Variant names:

• chr7-18935100-T-G
• rs10248565
• NM_178425.4:c.2804-709T>G

Variant summary

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

The NM_178425.4(HDAC9):​c.2804-709T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,090 control chromosomes in the GnomAD database, including 1,744 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 0.14 (1744 hom., cov: 32)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC9	NM_178425.4	c.2804-709T>G		intron_variant	Intron 22 of 25	ENST00000686413.1	NP_848512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000686413.1	c.2804-709T>G		intron_variant	Intron 22 of 25		NM_178425.4	ENSP00000509161.1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21111 AN: 151972 Hom.: 1744 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0946

Gnomad ASJ AF: 0.0887

Gnomad EAS AF: 0.00773

Gnomad SAS AF: 0.0508

Gnomad FIN AF: 0.0962

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.139 AC: 21136 AN: 152090 Hom.: 1744 Cov.: 32 AF XY: 0.134 AC XY: 9999 AN XY: 74356

African (AFR) AF: 0.216 AC: 8979 AN: 41488

American (AMR) AF: 0.0945 AC: 1444 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0887 AC: 308 AN: 3472

East Asian (EAS) AF: 0.00775 AC: 40 AN: 5162

South Asian (SAS) AF: 0.0505 AC: 243 AN: 4816

European-Finnish (FIN) AF: 0.0962 AC: 1019 AN: 10588

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8683 AN: 67970

Other (OTH) AF: 0.131 AC: 277 AN: 2112

Alfa AF: 0.125 Hom.: 2580

Bravo AF: 0.143

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	-0.90
CADD	Benign	5.1
DANN	Benign	0.78
PhyloP100		0.30
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: rs10248565; hg19: chr7-18974723;