chr17-44114525-G-T

Variant names:

• chr17-44114525-G-T
• rs228768
• NM_005474.5:c.22+2969C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005474.5(HDAC5):​c.22+2969C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,074 control chromosomes in the GnomAD database, including 23,870 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 0.50 (23870 hom., cov: 32)
• Consequence: HDAC5 NM_005474.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64
• Publications: 13 publications found

Genes affected

HDAC5 (HGNC:14068): (histone deacetylase 5) 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 belongs to the class II histone deacetylase/acuc/apha family. It possesses histone deacetylase activity and represses transcription when tethered to a promoter. It coimmunoprecipitates only with HDAC3 family member and might form multicomplex proteins. It also interacts with myocyte enhancer factor-2 (MEF2) proteins, resulting in repression of MEF2-dependent genes. This gene is thought to be associated with colon cancer. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

HDAC5 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC5	NM_005474.5	c.22+2969C>A		intron_variant	Intron 2 of 26	ENST00000682912.1	NP_005465.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC5	ENST00000682912.1	c.22+2969C>A		intron_variant	Intron 2 of 26		NM_005474.5	ENSP00000507606.1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76203 AN: 151952 Hom.: 23872 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.501 AC: 76193 AN: 152074 Hom.: 23870 Cov.: 32 AF XY: 0.504 AC XY: 37490 AN XY: 74336

African (AFR) AF: 0.128 AC: 5309 AN: 41522

American (AMR) AF: 0.536 AC: 8191 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1974 AN: 3466

East Asian (EAS) AF: 0.233 AC: 1197 AN: 5144

South Asian (SAS) AF: 0.710 AC: 3422 AN: 4822

European-Finnish (FIN) AF: 0.679 AC: 7172 AN: 10564

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.691 AC: 46924 AN: 67956

Other (OTH) AF: 0.540 AC: 1137 AN: 2106

Alfa AF: 0.593 Hom.: 5888

Bravo AF: 0.467

Asia WGS AF: 0.458 AC: 1592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Benign	0.71
PhyloP100		1.6
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: rs228768; hg19: chr17-42191893;