7-18935566-T-C

Variant names:

• chr7-18935566-T-C
• rs2240419
• NM_178425.4:c.2804-243T>C

Variant summary

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

The NM_178425.4(HDAC9):​c.2804-243T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 152,110 control chromosomes in the GnomAD database, including 49,449 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 0.80 (49449 hom., cov: 30)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124
• Publications: 15 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	NM_178425.4	MANE Select	c.2804-243T>C		intron	N/A	NP_848512.1	Q9UKV0-7
	HDAC9	NM_178423.3		c.2795-243T>C		intron	N/A	NP_848510.1	Q9UKV0-5
	HDAC9	NM_001321868.2		c.2729-243T>C		intron	N/A	NP_001308797.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	ENST00000686413.1	MANE Select	c.2804-243T>C		intron	N/A	ENSP00000509161.1	Q9UKV0-7
	HDAC9	ENST00000441542.7	TSL:1	c.2804-243T>C		intron	N/A	ENSP00000408617.2	Q9UKV0-7
	HDAC9	ENST00000406451.8	TSL:1	c.2795-243T>C		intron	N/A	ENSP00000384657.3	Q9UKV0-5

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122062 AN: 151992 Hom.: 49388 Cov.: 30

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.803 AC: 122184 AN: 152110 Hom.: 49449 Cov.: 30 AF XY: 0.805 AC XY: 59855 AN XY: 74350

African (AFR) AF: 0.907 AC: 37675 AN: 41524

American (AMR) AF: 0.790 AC: 12059 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2616 AN: 3472

East Asian (EAS) AF: 0.735 AC: 3780 AN: 5146

South Asian (SAS) AF: 0.849 AC: 4095 AN: 4822

European-Finnish (FIN) AF: 0.771 AC: 8160 AN: 10586

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.754 AC: 51244 AN: 67976

Other (OTH) AF: 0.773 AC: 1632 AN: 2110

Alfa AF: 0.766 Hom.: 97768

Bravo AF: 0.805

Asia WGS AF: 0.792 AC: 2755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.4
DANN	Benign	0.74
PhyloP100		-0.12
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: rs2240419; hg19: chr7-18975189;