chr7-18992312-C-T

Variant names:

• chr7-18992312-C-T
• rs11984041
• NM_178425.4:c.3171-3711C>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.3171-3711C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 151,882 control chromosomes in the GnomAD database, including 1,350 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 0.12 (1350 hom., cov: 33)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• Publications: 67 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 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.3171-3711C>T		intron	N/A	NP_848512.1
	HDAC9	NM_178423.3		c.3162-3711C>T		intron	N/A	NP_848510.1
	HDAC9	NM_001321868.2		c.3096-3711C>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.3171-3711C>T		intron	N/A	ENSP00000509161.1
	HDAC9	ENST00000441542.7	TSL:1	c.3171-3711C>T		intron	N/A	ENSP00000408617.2
	HDAC9	ENST00000406451.8	TSL:1	c.3162-3711C>T		intron	N/A	ENSP00000384657.3

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18696 AN: 151764 Hom.: 1349 Cov.: 33

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0969

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0943

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.123 AC: 18701 AN: 151882 Hom.: 1350 Cov.: 33 AF XY: 0.122 AC XY: 9060 AN XY: 74198

African (AFR) AF: 0.204 AC: 8425 AN: 41394

American (AMR) AF: 0.0877 AC: 1337 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 391 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5174

South Asian (SAS) AF: 0.0962 AC: 462 AN: 4804

European-Finnish (FIN) AF: 0.124 AC: 1303 AN: 10498

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0943 AC: 6413 AN: 67978

Other (OTH) AF: 0.109 AC: 229 AN: 2108

Alfa AF: 0.102 Hom.: 2863

Bravo AF: 0.124

Asia WGS AF: 0.0460 AC: 162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.061
DANN	Benign	0.39
PhyloP100		-2.2
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: rs11984041; hg19: chr7-19031935;