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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005474.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HDAC5	NM_005474.5	MANE Select	c.22+1677C>G	intron	N/A	NP_005465.2
HDAC5	NM_001015053.2		c.22+1677C>G	intron	N/A	NP_001015053.1
HDAC5	NM_001382393.1		c.22+1677C>G	intron	N/A	NP_001369322.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HDAC5	ENST00000682912.1	MANE Select	c.22+1677C>G	intron	N/A	ENSP00000507606.1
HDAC5	ENST00000586802.5	TSL:1	c.22+1677C>G	intron	N/A	ENSP00000468004.1
HDAC5	ENST00000336057.9	TSL:1	c.22+1677C>G	intron	N/A	ENSP00000337290.4

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over