rs12666612

chr7-18335622-T-C

Variant summary

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

The NM_001321868.2(HDAC9):c.26-160640T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 151,638 control chromosomes in the GnomAD database, including 728 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 0.087 (728 hom., cov: 32)
• Consequence: HDAC9 NM_001321868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.915

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDAC9	NM_001204144.3	c.26-123220T>C		intron_variant
HDAC9	NM_001321868.2	c.26-160640T>C		intron_variant
HDAC9	NM_001321869.2	c.26-160640T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC9	ENST00000413509.6	c.-42+45107T>C		intron_variant		5
HDAC9	ENST00000417496.6	c.26-123220T>C		intron_variant		2
HDAC9	ENST00000433709.6	c.-111+45107T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0864 AC: 13094 AN: 151520 Hom.: 719 Cov.: 32

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0884

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0970

Gnomad OTH AF: 0.0851

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

GnomAD4 genome AF: 0.0866 AC: 13130 AN: 151638 Hom.: 728 Cov.: 32 AF XY: 0.0908 AC XY: 6729 AN XY: 74100

Gnomad4 AFR AF: 0.0367

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.0884

Gnomad4 NFE AF: 0.0970

Gnomad4 OTH AF: 0.0871

Alfa AF: 0.0920 Hom.: 383

Bravo AF: 0.0857

Asia WGS AF: 0.166 AC: 576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.76
Dann	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12666612; hg19: chr7-18375245;