rs17350383

Variant names:

• chr7-18890590-C-T
• rs17350383
• NM_178425.4:c.2803+15994C>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.2803+15994C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,160 control chromosomes in the GnomAD database, including 1,830 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 0.14 (1830 hom., cov: 32)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670
• Publications: 5 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-AS1 (HGNC:40664): (HDAC9 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC9	NM_178425.4	c.2803+15994C>T		intron_variant	Intron 22 of 25	ENST00000686413.1	NP_848512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000686413.1	c.2803+15994C>T		intron_variant	Intron 22 of 25		NM_178425.4	ENSP00000509161.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21314 AN: 152042 Hom.: 1827 Cov.: 32

Gnomad AFR AF: 0.0351

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.140 AC: 21326 AN: 152160 Hom.: 1830 Cov.: 32 AF XY: 0.143 AC XY: 10659 AN XY: 74372

African (AFR) AF: 0.0350 AC: 1453 AN: 41522

American (AMR) AF: 0.193 AC: 2955 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 632 AN: 3466

East Asian (EAS) AF: 0.129 AC: 668 AN: 5168

South Asian (SAS) AF: 0.252 AC: 1216 AN: 4824

European-Finnish (FIN) AF: 0.187 AC: 1980 AN: 10578

Middle Eastern (MID) AF: 0.114 AC: 33 AN: 290

European-Non Finnish (NFE) AF: 0.175 AC: 11919 AN: 68006

Other (OTH) AF: 0.148 AC: 312 AN: 2114

Alfa AF: 0.173 Hom.: 1208

Bravo AF: 0.133

Asia WGS AF: 0.209 AC: 724 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.60
PhyloP100		0.067
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: rs17350383; hg19: chr7-18930213;