7-18760790-G-T

Variant names:

• chr7-18760790-G-T
• rs11764116
• NM_178425.4:c.2044-1367G>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.2044-1367G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,086 control chromosomes in the GnomAD database, including 4,691 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 0.23 (4691 hom., cov: 33)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 16 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 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.2044-1367G>T		intron	N/A	NP_848512.1
	HDAC9	NM_178423.3		c.2035-1367G>T		intron	N/A	NP_848510.1
	HDAC9	NM_001321868.2		c.1969-1367G>T		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.2044-1367G>T		intron	N/A	ENSP00000509161.1
	HDAC9	ENST00000441542.7	TSL:1	c.2044-1367G>T		intron	N/A	ENSP00000408617.2
	HDAC9	ENST00000406451.8	TSL:1	c.2035-1367G>T		intron	N/A	ENSP00000384657.3

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35247 AN: 151968 Hom.: 4682 Cov.: 33

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.232 AC: 35287 AN: 152086 Hom.: 4691 Cov.: 33 AF XY: 0.237 AC XY: 17644 AN XY: 74340

African (AFR) AF: 0.197 AC: 8167 AN: 41516

American (AMR) AF: 0.250 AC: 3815 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 629 AN: 3466

East Asian (EAS) AF: 0.632 AC: 3251 AN: 5144

South Asian (SAS) AF: 0.349 AC: 1678 AN: 4810

European-Finnish (FIN) AF: 0.232 AC: 2454 AN: 10572

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14321 AN: 67984

Other (OTH) AF: 0.222 AC: 469 AN: 2116

Alfa AF: 0.225 Hom.: 9113

Bravo AF: 0.233

Asia WGS AF: 0.434 AC: 1507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	15
DANN	Benign	0.74
PhyloP100		1.5
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: rs11764116; hg19: chr7-18800413;