7-18407701-G-C

Variant names:

• chr7-18407701-G-C
• rs2012064
• NM_001321868.2:c.26-88561G>C

Variant summary

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

The NM_001321868.2(HDAC9):​c.26-88561G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 152,076 control chromosomes in the GnomAD database, including 42,537 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 0.75 (42537 hom., cov: 32)
• Consequence: HDAC9 NM_001321868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC9	NM_001321868.2	c.26-88561G>C		intron_variant	Intron 2 of 25		NP_001308797.1
HDAC9	NM_001321869.2	c.26-88561G>C		intron_variant	Intron 2 of 12		NP_001308798.1
HDAC9	NM_001321870.2	c.26-88561G>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.26-51141G>C		intron_variant	Intron 2 of 12	2		ENSP00000401669.2
HDAC9	ENST00000707077.1	c.26-88561G>C		intron_variant	Intron 2 of 11			ENSP00000516728.1
HDAC9	ENST00000413509.6	c.-41-88561G>C		intron_variant	Intron 1 of 3	5		ENSP00000412497.2

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113465 AN: 151958 Hom.: 42483 Cov.: 32

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.747 AC: 113574 AN: 152076 Hom.: 42537 Cov.: 32 AF XY: 0.750 AC XY: 55751 AN XY: 74326

African (AFR) AF: 0.715 AC: 29677 AN: 41490

American (AMR) AF: 0.734 AC: 11212 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.773 AC: 2683 AN: 3470

East Asian (EAS) AF: 0.799 AC: 4136 AN: 5178

South Asian (SAS) AF: 0.829 AC: 3984 AN: 4806

European-Finnish (FIN) AF: 0.744 AC: 7864 AN: 10566

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.757 AC: 51427 AN: 67972

Other (OTH) AF: 0.758 AC: 1600 AN: 2112

Alfa AF: 0.684 Hom.: 2284

Bravo AF: 0.745

Asia WGS AF: 0.778 AC: 2705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.5
DANN	Benign	0.67
PhyloP100		-0.17
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: rs2012064; hg19: chr7-18447324;