7-18632761-G-T

Variant names:

• chr7-18632761-G-T
• rs801540
• NM_178425.4:c.797-1866G>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.797-1866G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 151,774 control chromosomes in the GnomAD database, including 32,945 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 0.66 (32945 hom., cov: 31)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 7 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 (EAS) allele frequency at 95% confidence interval = 0.755 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.797-1866G>T		intron	N/A	NP_848512.1
	HDAC9	NM_178423.3		c.788-1866G>T		intron	N/A	NP_848510.1
	HDAC9	NM_001321868.2		c.722-1866G>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.797-1866G>T		intron	N/A	ENSP00000509161.1
	HDAC9	ENST00000441542.7	TSL:1	c.797-1866G>T		intron	N/A	ENSP00000408617.2
	HDAC9	ENST00000406451.8	TSL:1	c.788-1866G>T		intron	N/A	ENSP00000384657.3

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99346 AN: 151654 Hom.: 32898 Cov.: 31

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.655 AC: 99457 AN: 151774 Hom.: 32945 Cov.: 31 AF XY: 0.655 AC XY: 48553 AN XY: 74144

African (AFR) AF: 0.756 AC: 31331 AN: 41430

American (AMR) AF: 0.662 AC: 10069 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2230 AN: 3470

East Asian (EAS) AF: 0.775 AC: 3975 AN: 5126

South Asian (SAS) AF: 0.734 AC: 3528 AN: 4806

European-Finnish (FIN) AF: 0.543 AC: 5722 AN: 10538

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40603 AN: 67872

Other (OTH) AF: 0.640 AC: 1350 AN: 2110

Alfa AF: 0.621 Hom.: 128916

Bravo AF: 0.667

Asia WGS AF: 0.776 AC: 2695 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.23
DANN	Benign	0.30
PhyloP100		-1.1
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: rs801540; hg19: chr7-18672384;