7-18940644-A-G

Variant names:

• chr7-18940644-A-G
• rs2853552
• NM_178425.4:c.2937+4702A>G

Variant summary

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

The NM_178425.4(HDAC9):​c.2937+4702A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 152,030 control chromosomes in the GnomAD database, including 41,682 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 0.74 (41682 hom., cov: 32)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.800
• Publications: 11 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 = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC9	NM_178425.4	c.2937+4702A>G		intron_variant	Intron 23 of 25	ENST00000686413.1	NP_848512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000686413.1	c.2937+4702A>G		intron_variant	Intron 23 of 25		NM_178425.4	ENSP00000509161.1

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112367 AN: 151912 Hom.: 41637 Cov.: 32

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.710

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

GnomAD4 genome AF: 0.740 AC: 112476 AN: 152030 Hom.: 41682 Cov.: 32 AF XY: 0.741 AC XY: 55100 AN XY: 74310

African (AFR) AF: 0.787 AC: 32646 AN: 41502

American (AMR) AF: 0.726 AC: 11092 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 2522 AN: 3466

East Asian (EAS) AF: 0.708 AC: 3648 AN: 5156

South Asian (SAS) AF: 0.818 AC: 3949 AN: 4828

European-Finnish (FIN) AF: 0.701 AC: 7397 AN: 10558

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48891 AN: 67934

Other (OTH) AF: 0.714 AC: 1507 AN: 2112

Alfa AF: 0.726 Hom.: 125288

Bravo AF: 0.739

Asia WGS AF: 0.775 AC: 2692 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	3.1
DANN	Benign	0.37
PhyloP100		-0.80
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: rs2853552; hg19: chr7-18980267;