rs12155400

Positions:

• chr7-18389298-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001321868.2(HDAC9):​c.26-106964A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0294 in 152,298 control chromosomes in the GnomAD database, including 95 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 0.029 (95 hom., cov: 31)
• Consequence: HDAC9 NM_001321868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118

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=-0.88).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0294 (4470/152298) while in subpopulation SAS AF= 0.0514 (248/4828). AF 95% confidence interval is 0.0461. There are 95 homozygotes in gnomad4. There are 2239 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4470 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDAC9	NM_001204144.3	c.26-69544A>G		intron_variant			NP_001191073.1
HDAC9	NM_001321868.2	c.26-106964A>G		intron_variant			NP_001308797.1
HDAC9	NM_001321869.2	c.26-106964A>G		intron_variant			NP_001308798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000413509.6	c.-42+98783A>G		intron_variant		5		ENSP00000412497
HDAC9	ENST00000417496.6	c.26-69544A>G		intron_variant		2		ENSP00000401669
HDAC9	ENST00000433709.6	c.-110-5817A>G		intron_variant		3		ENSP00000409003

Frequencies

GnomAD3 genomes AF: 0.0294 AC: 4467 AN: 152180 Hom.: 95 Cov.: 31

Gnomad AFR AF: 0.00825

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0457

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.0591

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0352

Gnomad OTH AF: 0.0249

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

GnomAD4 genome AF: 0.0294 AC: 4470 AN: 152298 Hom.: 95 Cov.: 31 AF XY: 0.0301 AC XY: 2239 AN XY: 74476

Gnomad4 AFR AF: 0.00823

Gnomad4 AMR AF: 0.0459

Gnomad4 ASJ AF: 0.0233

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0514

Gnomad4 FIN AF: 0.0591

Gnomad4 NFE AF: 0.0352

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0315 Hom.: 13

Bravo AF: 0.0286

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12155400; hg19: chr7-18428921;