Genetic Variant HDAC5:c.22+1677C>G (chr17-44115817-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005474.5(HDAC5):c.22+1677C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 152,090 control chromosomes in the GnomAD database, including 35,305 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 0.67 ( 35291 hom., cov: 31)

Exomes 𝑓: 0.77 ( 14 hom. )

Consequence

HDAC5
NM_005474.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0470

Publications

39 publications found

Variant links:

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)

HDAC5 links:

ENSG00000267638 (HGNC:):

ENSG00000267638 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC5	NM_005474.5 link	c.22+1677C>G		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 link	c.22+1677C>G		intron_variant	Intron 2 of 26		NM_005474.5	ENSP00000507606.1

Frequencies

GnomAD3 genomes

AF:

0.668

AC:

101426

AN:

151928

Hom.:

35290

Cov.:

show subpopulations

Gnomad AFR

AF:

0.478

Gnomad AMI

AF:

0.826

Gnomad AMR

AF:

0.694

Gnomad ASJ

AF:

0.676

Gnomad EAS

AF:

0.369

Gnomad SAS

AF:

0.786

Gnomad FIN

AF:

0.723

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.779

Gnomad OTH

AF:

0.691

GnomAD4 exome

AF:

0.773

AC:

AN:

Hom.:

AF XY:

0.781

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.789

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.667

AC:

101457

AN:

152046

Hom.:

35291

Cov.:

AF XY:

0.666

AC XY:

49514

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.478

AC:

19813

AN:

41448

American (AMR)

AF:

0.693

AC:

10587

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.676

AC:

2345

AN:

3470

East Asian (EAS)

AF:

0.369

AC:

1896

AN:

5138

South Asian (SAS)

AF:

0.786

AC:

3789

AN:

4820

European-Finnish (FIN)

AF:

0.723

AC:

7663

AN:

10594

Middle Eastern (MID)

AF:

0.779

AC:

229

AN:

294

European-Non Finnish (NFE)

AF:

0.779

AC:

52923

AN:

67980

Other (OTH)

AF:

0.693

AC:

1459

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1631

3262

4892

6523

8154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

802

1604

2406

3208

4010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.739

Hom.:

20745

Bravo

AF:

0.651

Asia WGS

AF:

0.609

AC:

2117

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

-0.047

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over