rs2073963

Positions:

• chr7-18838251-T-G

Variant summary

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

The NM_178425.4(HDAC9):​c.2684+2254T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,806 control chromosomes in the GnomAD database, including 14,205 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 0.43 (14205 hom., cov: 32)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDAC9	NM_178425.4	c.2684+2254T>G		intron_variant		ENST00000686413.1	NP_848512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000686413.1	c.2684+2254T>G		intron_variant			NM_178425.4	ENSP00000509161	P4

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65353 AN: 151686 Hom.: 14181 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.431 AC: 65423 AN: 151806 Hom.: 14205 Cov.: 32 AF XY: 0.435 AC XY: 32252 AN XY: 74206

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.425

Alfa AF: 0.400 Hom.: 25054

Bravo AF: 0.429

Asia WGS AF: 0.516 AC: 1793 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	2.2
DANN	Benign	0.41

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: rs2073963; hg19: chr7-18877874;