rs11984041

chr7-18992312-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178425.4(HDAC9):c.3171-3711C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 151,882 control chromosomes in the GnomAD database, including 1,350 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 0.12 (1350 hom., cov: 33)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDAC9	NM_178425.4	c.3171-3711C>T		intron_variant		ENST00000686413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC9	ENST00000686413.1	c.3171-3711C>T		intron_variant			NM_178425.4	P4

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18696 AN: 151764 Hom.: 1349 Cov.: 33

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0969

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0943

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.123 AC: 18701 AN: 151882 Hom.: 1350 Cov.: 33 AF XY: 0.122 AC XY: 9060 AN XY: 74198

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.0877

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0962

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.0943

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0984 Hom.: 1049

Bravo AF: 0.124

Asia WGS AF: 0.0460 AC: 162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.061
Dann	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs11984041; hg19: chr7-19031935;