rs1726610

Variant names:

• chr7-18590585-A-C
• rs1726610
• NM_178425.4:c.415+99A>C

Your query was ambiguous. Multiple possible variants found:

• chr7-18590585-A-C
• chr7-18590585-A-G
• chr7-18590585-A-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.415+99A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 1,183,904 control chromosomes in the GnomAD database, including 257,477 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 0.66 (32907 hom., cov: 31)
  • Exomes 𝑓: 0.66 (224570 hom.)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259
• 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 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.415+99A>C		intron	N/A	NP_848512.1	Q9UKV0-7
	HDAC9	NM_178423.3		c.406+99A>C		intron	N/A	NP_848510.1	Q9UKV0-5
	HDAC9	NM_001321868.2		c.472+99A>C		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.415+99A>C		intron	N/A	ENSP00000509161.1	Q9UKV0-7
	HDAC9	ENST00000441542.7	TSL:1	c.415+99A>C		intron	N/A	ENSP00000408617.2	Q9UKV0-7
	HDAC9	ENST00000406451.8	TSL:1	c.406+99A>C		intron	N/A	ENSP00000384657.3	Q9UKV0-5

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99581 AN: 151908 Hom.: 32855 Cov.: 31

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.861

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.670

GnomAD4 exome AF: 0.657 AC: 677885 AN: 1031878 Hom.: 224570 AF XY: 0.660 AC XY: 336436 AN XY: 509790

African (AFR) AF: 0.632 AC: 14452 AN: 22872

American (AMR) AF: 0.691 AC: 14006 AN: 20266

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 12852 AN: 17910

East Asian (EAS) AF: 0.884 AC: 29663 AN: 33572

South Asian (SAS) AF: 0.765 AC: 40176 AN: 52524

European-Finnish (FIN) AF: 0.629 AC: 28448 AN: 45220

Middle Eastern (MID) AF: 0.700 AC: 2969 AN: 4244

European-Non Finnish (NFE) AF: 0.639 AC: 505300 AN: 790304

Other (OTH) AF: 0.668 AC: 30019 AN: 44966

GnomAD4 genome AF: 0.656 AC: 99694 AN: 152026 Hom.: 32907 Cov.: 31 AF XY: 0.659 AC XY: 48966 AN XY: 74302

African (AFR) AF: 0.629 AC: 26054 AN: 41430

American (AMR) AF: 0.687 AC: 10491 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2452 AN: 3468

East Asian (EAS) AF: 0.861 AC: 4459 AN: 5178

South Asian (SAS) AF: 0.775 AC: 3737 AN: 4820

European-Finnish (FIN) AF: 0.637 AC: 6734 AN: 10564

Middle Eastern (MID) AF: 0.702 AC: 205 AN: 292

European-Non Finnish (NFE) AF: 0.642 AC: 43635 AN: 67988

Other (OTH) AF: 0.676 AC: 1426 AN: 2110

Alfa AF: 0.649 Hom.: 95353

Bravo AF: 0.657

Asia WGS AF: 0.835 AC: 2900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.9
DANN	Benign	0.59
PhyloP100		0.26
Mutation Taster		=30/70	disease causing

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: rs1726610; hg19: chr7-18630208; COSMIC: COSV67783566; COSMIC: COSV67783566;