7-18814978-T-A

Position:

• chr7-18814978-T-A

Variant summary

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

The NM_178425.4(HDAC9):​c.2323-14183T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,040 control chromosomes in the GnomAD database, including 18,403 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 0.45 (18403 hom., cov: 32)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDAC9	NM_178425.4	c.2323-14183T>A		intron_variant		ENST00000686413.1	NP_848512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000686413.1	c.2323-14183T>A		intron_variant			NM_178425.4	ENSP00000509161	P4

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68613 AN: 151922 Hom.: 18369 Cov.: 32

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.0917

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.452 AC: 68704 AN: 152040 Hom.: 18403 Cov.: 32 AF XY: 0.449 AC XY: 33369 AN XY: 74312

Gnomad4 AFR AF: 0.753

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.0921

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.412

Alfa AF: 0.416 Hom.: 1827

Bravo AF: 0.463

Asia WGS AF: 0.303 AC: 1046 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.82
DANN	Benign	0.66

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: rs10269422; hg19: chr7-18854601;