rs1726610

Positions:

• chr7-18590585-A-C
• chr7-18590585-A-G
• chr7-18590585-A-T

Variant summary

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

The NM_178425.4(HDAC9):​c.415+99A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 1,183,904 control chromosomes in the GnomAD database, including 257,477 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 0.66 (32907 hom., cov: 31)
  • Exomes 𝑓: 0.66 (224570 hom.)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDAC9	NM_178425.4	c.415+99A>C		intron_variant		ENST00000686413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC9	ENST00000686413.1	c.415+99A>C		intron_variant			NM_178425.4	P4

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99581 AN: 151908 Hom.: 32855 Cov.: 31

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.861

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.670

GnomAD4 exome AF: 0.657 AC: 677885 AN: 1031878 Hom.: 224570 AF XY: 0.660 AC XY: 336436 AN XY: 509790

Gnomad4 AFR exome AF: 0.632

Gnomad4 AMR exome AF: 0.691

Gnomad4 ASJ exome AF: 0.718

Gnomad4 EAS exome AF: 0.884

Gnomad4 SAS exome AF: 0.765

Gnomad4 FIN exome AF: 0.629

Gnomad4 NFE exome AF: 0.639

Gnomad4 OTH exome AF: 0.668

GnomAD4 genome AF: 0.656 AC: 99694 AN: 152026 Hom.: 32907 Cov.: 31 AF XY: 0.659 AC XY: 48966 AN XY: 74302

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.687

Gnomad4 ASJ AF: 0.707

Gnomad4 EAS AF: 0.861

Gnomad4 SAS AF: 0.775

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.676

Alfa AF: 0.647 Hom.: 40827

Bravo AF: 0.657

Asia WGS AF: 0.835 AC: 2900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.9
DANN	Benign	0.59

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: rs1726610; hg19: chr7-18630208; COSMIC: COSV67783566; COSMIC: COSV67783566;