rs12540872

Variant names:

• chr7-18797044-G-A
• rs12540872
• NM_178425.4:c.2322+3592G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-18797044-G-A
• chr7-18797044-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178425.4(HDAC9):​c.2322+3592G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,084 control chromosomes in the GnomAD database, including 14,296 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 0.41 (14296 hom., cov: 33)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161
• Publications: 2 publications found

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]

HDAC9 Gene-Disease associations (from GenCC):

• auriculocondylar syndrome 4

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC9	NM_178425.4	c.2322+3592G>A		intron_variant	Intron 17 of 25	ENST00000686413.1	NP_848512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000686413.1	c.2322+3592G>A		intron_variant	Intron 17 of 25		NM_178425.4	ENSP00000509161.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62797 AN: 151966 Hom.: 14299 Cov.: 33

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.413 AC: 62800 AN: 152084 Hom.: 14296 Cov.: 33 AF XY: 0.412 AC XY: 30638 AN XY: 74330

African (AFR) AF: 0.204 AC: 8466 AN: 41504

American (AMR) AF: 0.433 AC: 6604 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1635 AN: 3468

East Asian (EAS) AF: 0.369 AC: 1911 AN: 5174

South Asian (SAS) AF: 0.491 AC: 2372 AN: 4828

European-Finnish (FIN) AF: 0.447 AC: 4718 AN: 10556

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.525 AC: 35671 AN: 67970

Other (OTH) AF: 0.442 AC: 934 AN: 2112

Alfa AF: 0.477 Hom.: 47441

Bravo AF: 0.400

Asia WGS AF: 0.417 AC: 1451 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.3
DANN	Benign	0.78
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12540872; hg19: chr7-18836667;