rs213273

Positions:

• chr7-18464885-G-A
• chr7-18464885-G-C

Variant summary

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

The NM_001321868.2(HDAC9):​c.26-31377G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.962 in 152,092 control chromosomes in the GnomAD database, including 70,321 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 0.96 (70321 hom., cov: 31)
• Consequence: HDAC9 NM_001321868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDAC9	NM_001204144.3	c.85+5984G>A		intron_variant			NP_001191073.1
HDAC9	NM_001321868.2	c.26-31377G>A		intron_variant			NP_001308797.1
HDAC9	NM_001321869.2	c.26-31377G>A		intron_variant			NP_001308798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000413509.6	c.-41-31377G>A		intron_variant		5		ENSP00000412497
HDAC9	ENST00000417496.6	c.85+5984G>A		intron_variant		2		ENSP00000401669
HDAC9	ENST00000433709.6	c.-41-31377G>A		intron_variant		3		ENSP00000409003

Frequencies

GnomAD3 genomes AF: 0.961 AC: 146117 AN: 151974 Hom.: 70259 Cov.: 31

Gnomad AFR AF: 0.983

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.979

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.940

Gnomad FIN AF: 0.979

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.943

Gnomad OTH AF: 0.959

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

GnomAD4 genome AF: 0.962 AC: 146239 AN: 152092 Hom.: 70321 Cov.: 31 AF XY: 0.963 AC XY: 71575 AN XY: 74348

Gnomad4 AFR AF: 0.983

Gnomad4 AMR AF: 0.965

Gnomad4 ASJ AF: 0.979

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.940

Gnomad4 FIN AF: 0.979

Gnomad4 NFE AF: 0.943

Gnomad4 OTH AF: 0.960

Alfa AF: 0.945 Hom.: 89181

Bravo AF: 0.961

Asia WGS AF: 0.974 AC: 3381 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.40
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs213273; hg19: chr7-18504508;