rs957960

Variant names:

• chr7-18837785-C-A
• rs957960
• NM_178425.4:c.2684+1788C>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.2684+1788C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,836 control chromosomes in the GnomAD database, including 13,381 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 0.42 (13381 hom., cov: 32)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.973
• Publications: 9 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC9	NM_178425.4	c.2684+1788C>A		intron_variant	Intron 21 of 25	ENST00000686413.1	NP_848512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000686413.1	c.2684+1788C>A		intron_variant	Intron 21 of 25		NM_178425.4	ENSP00000509161.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63263 AN: 151718 Hom.: 13358 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.417 AC: 63331 AN: 151836 Hom.: 13381 Cov.: 32 AF XY: 0.421 AC XY: 31260 AN XY: 74212

African (AFR) AF: 0.475 AC: 19690 AN: 41426

American (AMR) AF: 0.395 AC: 6011 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1410 AN: 3466

East Asian (EAS) AF: 0.476 AC: 2459 AN: 5170

South Asian (SAS) AF: 0.550 AC: 2648 AN: 4812

European-Finnish (FIN) AF: 0.400 AC: 4226 AN: 10552

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.374 AC: 25401 AN: 67884

Other (OTH) AF: 0.416 AC: 878 AN: 2110

Alfa AF: 0.398 Hom.: 2060

Bravo AF: 0.416

Asia WGS AF: 0.501 AC: 1741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.7
DANN	Benign	0.30
PhyloP100		0.97
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: rs957960; hg19: chr7-18877408;