rs756853

Variant names:

• chr7-18850377-G-A
• rs756853
• NM_178425.4:c.2684+14380G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-18850377-G-A
• chr7-18850377-G-C

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+14380G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 151,974 control chromosomes in the GnomAD database, including 23,324 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 0.55 (23324 hom., cov: 32)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.714
• Publications: 22 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.578 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	NM_178425.4	MANE Select	c.2684+14380G>A		intron	N/A	NP_848512.1	Q9UKV0-7
	HDAC9	NM_178423.3		c.2675+14380G>A		intron	N/A	NP_848510.1	Q9UKV0-5
	HDAC9	NM_001321868.2		c.2609+14380G>A		intron	N/A	NP_001308797.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	ENST00000686413.1	MANE Select	c.2684+14380G>A		intron	N/A	ENSP00000509161.1	Q9UKV0-7
	HDAC9	ENST00000441542.7	TSL:1	c.2684+14380G>A		intron	N/A	ENSP00000408617.2	Q9UKV0-7
	HDAC9	ENST00000406451.8	TSL:1	c.2675+14380G>A		intron	N/A	ENSP00000384657.3	Q9UKV0-5

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84100 AN: 151856 Hom.: 23311 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.554 AC: 84154 AN: 151974 Hom.: 23324 Cov.: 32 AF XY: 0.549 AC XY: 40755 AN XY: 74258

African (AFR) AF: 0.543 AC: 22501 AN: 41460

American (AMR) AF: 0.535 AC: 8162 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1956 AN: 3470

East Asian (EAS) AF: 0.465 AC: 2399 AN: 5162

South Asian (SAS) AF: 0.397 AC: 1912 AN: 4814

European-Finnish (FIN) AF: 0.557 AC: 5868 AN: 10542

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39609 AN: 67956

Other (OTH) AF: 0.548 AC: 1160 AN: 2116

Alfa AF: 0.568 Hom.: 46747

Bravo AF: 0.554

Asia WGS AF: 0.441 AC: 1535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.66
DANN	Benign	0.73
PhyloP100		-0.71
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: rs756853; hg19: chr7-18890000;