7-18814978-T-A

Variant names:

• chr7-18814978-T-A
• rs10269422
• NM_178425.4:c.2323-14183T>A

Variant summary

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

The NM_178425.4(HDAC9):​c.2323-14183T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,040 control chromosomes in the GnomAD database, including 18,403 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 0.45 (18403 hom., cov: 32)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178425.4. 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.2323-14183T>A		intron	N/A	NP_848512.1
	HDAC9	NM_178423.3		c.2314-14183T>A		intron	N/A	NP_848510.1
	HDAC9	NM_001321868.2		c.2248-14183T>A		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.2323-14183T>A		intron	N/A	ENSP00000509161.1
	HDAC9	ENST00000441542.7	TSL:1	c.2323-14183T>A		intron	N/A	ENSP00000408617.2
	HDAC9	ENST00000406451.8	TSL:1	c.2314-14183T>A		intron	N/A	ENSP00000384657.3

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68613 AN: 151922 Hom.: 18369 Cov.: 32

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.0917

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.452 AC: 68704 AN: 152040 Hom.: 18403 Cov.: 32 AF XY: 0.449 AC XY: 33369 AN XY: 74312

African (AFR) AF: 0.753 AC: 31251 AN: 41480

American (AMR) AF: 0.373 AC: 5698 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1466 AN: 3470

East Asian (EAS) AF: 0.0921 AC: 477 AN: 5180

South Asian (SAS) AF: 0.370 AC: 1784 AN: 4816

European-Finnish (FIN) AF: 0.402 AC: 4234 AN: 10542

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22505 AN: 67958

Other (OTH) AF: 0.412 AC: 865 AN: 2102

Alfa AF: 0.416 Hom.: 1827

Bravo AF: 0.463

Asia WGS AF: 0.303 AC: 1046 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.82
DANN	Benign	0.66
PhyloP100		-0.21
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: rs10269422; hg19: chr7-18854601;