rs12700014

Variant names:

• chr7-18924453-A-G
• rs12700014
• NM_178425.4:c.2804-11356A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000686413.1(HDAC9):​c.2804-11356A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 151,830 control chromosomes in the GnomAD database, including 15,072 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 0.44 (15072 hom., cov: 32)
• Consequence: HDAC9 ENST00000686413.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.54
• Publications: 6 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000686413.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	NM_178425.4	MANE Select	c.2804-11356A>G		intron	N/A	NP_848512.1
	HDAC9	NM_178423.3		c.2795-11356A>G		intron	N/A	NP_848510.1
	HDAC9	NM_001321868.2		c.2729-11356A>G		intron	N/A	NP_001308797.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	ENST00000686413.1	MANE Select	c.2804-11356A>G		intron	N/A	ENSP00000509161.1
	HDAC9	ENST00000441542.7	TSL:1	c.2804-11356A>G		intron	N/A	ENSP00000408617.2
	HDAC9	ENST00000406451.8	TSL:1	c.2795-11356A>G		intron	N/A	ENSP00000384657.3

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66510 AN: 151712 Hom.: 15076 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.438 AC: 66511 AN: 151830 Hom.: 15072 Cov.: 32 AF XY: 0.434 AC XY: 32196 AN XY: 74200

African (AFR) AF: 0.412 AC: 17074 AN: 41436

American (AMR) AF: 0.385 AC: 5868 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1791 AN: 3468

East Asian (EAS) AF: 0.239 AC: 1234 AN: 5164

South Asian (SAS) AF: 0.305 AC: 1468 AN: 4816

European-Finnish (FIN) AF: 0.459 AC: 4832 AN: 10524

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.482 AC: 32734 AN: 67874

Other (OTH) AF: 0.442 AC: 935 AN: 2116

Alfa AF: 0.461 Hom.: 47410

Bravo AF: 0.432

Asia WGS AF: 0.277 AC: 966 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Benign	0.66
PhyloP100		3.5
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: rs12700014; hg19: chr7-18964076;