rs1178355

Variant names:

• chr7-18165188-A-C
• rs1178355
• NM_001321868.2:c.25+2839A>C

Your query was ambiguous. Multiple possible variants found:

• chr7-18165188-A-C
• chr7-18165188-A-G
• chr7-18165188-A-T

Variant summary

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

The NM_001321868.2(HDAC9):​c.25+2839A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,962 control chromosomes in the GnomAD database, including 16,050 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 0.43 (16050 hom., cov: 32)
• Consequence: HDAC9 NM_001321868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.782
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC9	NM_001321868.2	c.25+2839A>C		intron_variant	Intron 2 of 25		NP_001308797.1
HDAC9	NM_001321869.2	c.25+2839A>C		intron_variant	Intron 2 of 12		NP_001308798.1
HDAC9	NM_001321870.2	c.25+2839A>C		intron_variant	Intron 2 of 12		NP_001308799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000417496.6	c.25+2839A>C		intron_variant	Intron 2 of 12	2		ENSP00000401669.2
HDAC9	ENST00000707077.1	c.25+2839A>C		intron_variant	Intron 2 of 11			ENSP00000516728.1
HDAC9	ENST00000425071.5	n.226+2839A>C		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65409 AN: 151842 Hom.: 16005 Cov.: 32

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.379

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

GnomAD4 genome AF: 0.431 AC: 65507 AN: 151962 Hom.: 16050 Cov.: 32 AF XY: 0.428 AC XY: 31799 AN XY: 74264

African (AFR) AF: 0.669 AC: 27710 AN: 41414

American (AMR) AF: 0.335 AC: 5113 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1220 AN: 3472

East Asian (EAS) AF: 0.495 AC: 2552 AN: 5158

South Asian (SAS) AF: 0.517 AC: 2491 AN: 4818

European-Finnish (FIN) AF: 0.299 AC: 3158 AN: 10558

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21976 AN: 67964

Other (OTH) AF: 0.382 AC: 807 AN: 2110

Alfa AF: 0.360 Hom.: 8148

Bravo AF: 0.442

Asia WGS AF: 0.512 AC: 1779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.99
DANN	Benign	0.66
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1178355; hg19: chr7-18204811;