rs1063639

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001378414.1(HDAC4):c.2580C>T(p.Pro860Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,613,816 control chromosomes in the GnomAD database, including 197,016 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 20770 hom., cov: 33)

Exomes 𝑓: 0.49 ( 176246 hom. )

Consequence

HDAC4
NM_001378414.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0730

Publications

27 publications found

Variant links:

Genes affected

HDAC4 (HGNC:14063): (histone deacetylase 4) 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 class II of the histone deacetylase/acuc/apha family. It possesses histone deacetylase activity and represses transcription when tethered to a promoter. This protein does not bind DNA directly, but through transcription factors MEF2C and MEF2D. It seems to interact in a multiprotein complex with RbAp48 and HDAC3. [provided by RefSeq, Jul 2008]

HDAC4 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with central hypotonia and dysmorphic facies
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
2q37 microdeletion syndrome
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

HDAC4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 2-239082174-G-A is Benign according to our data. Variant chr2-239082174-G-A is described in ClinVar as [Benign]. Clinvar id is 1174850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.073 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC4	NM_001378414.1 link	c.2580C>T	p.Pro860Pro	synonymous_variant	Exon 21 of 27	ENST00000543185.6	NP_001365343.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HDAC4	ENST00000543185.6 link	c.2580C>T	p.Pro860Pro	synonymous_variant	Exon 21 of 27	5	NM_001378414.1	ENSP00000440481.3	A0A7I2SVS4
HDAC4	ENST00000345617.7 link	c.2565C>T	p.Pro855Pro	synonymous_variant	Exon 21 of 27	1		ENSP00000264606.3	P56524-1
HDAC4	ENST00000487617.5 link	n.472C>T		non_coding_transcript_exon_variant	Exon 7 of 8	3
HDAC4	ENST00000690129.1 link	n.594C>T		non_coding_transcript_exon_variant	Exon 4 of 10

Frequencies

GnomAD3 genomes

AF:

0.519

AC:

78860

AN:

151966

Hom.:

20724

Cov.:

show subpopulations

Gnomad AFR

AF:

0.575

Gnomad AMI

AF:

0.420

Gnomad AMR

AF:

0.596

Gnomad ASJ

AF:

0.486

Gnomad EAS

AF:

0.693

Gnomad SAS

AF:

0.619

Gnomad FIN

AF:

0.458

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.460

Gnomad OTH

AF:

0.529

GnomAD2 exomes

AF:

0.537

AC:

134954

AN:

251476

AF XY:

0.533

show subpopulations

Gnomad AFR exome

AF:

0.566

Gnomad AMR exome

AF:

0.687

Gnomad ASJ exome

AF:

0.478

Gnomad EAS exome

AF:

0.684

Gnomad FIN exome

AF:

0.466

Gnomad NFE exome

AF:

0.463

Gnomad OTH exome

AF:

0.510

GnomAD4 exome

AF:

0.487

AC:

711312

AN:

1461732

Hom.:

176246

Cov.:

AF XY:

0.489

AC XY:

355241

AN XY:

727182

show subpopulations

African (AFR)

AF:

0.574

AC:

19206

AN:

33478

American (AMR)

AF:

0.679

AC:

30385

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.478

AC:

12481

AN:

26134

East Asian (EAS)

AF:

0.646

AC:

25644

AN:

39700

South Asian (SAS)

AF:

0.606

AC:

52310

AN:

86256

European-Finnish (FIN)

AF:

0.465

AC:

24853

AN:

53406

Middle Eastern (MID)

AF:

0.535

AC:

3083

AN:

5766

European-Non Finnish (NFE)

AF:

0.461

AC:

513041

AN:

1111876

Other (OTH)

AF:

0.502

AC:

30309

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

20877

41754

62630

83507

104384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.519

AC:

78962

AN:

152084

Hom.:

20770

Cov.:

AF XY:

0.524

AC XY:

38962

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.575

AC:

23866

AN:

41494

American (AMR)

AF:

0.597

AC:

9130

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.486

AC:

1683

AN:

3466

East Asian (EAS)

AF:

0.694

AC:

3564

AN:

5138

South Asian (SAS)

AF:

0.618

AC:

2986

AN:

4828

European-Finnish (FIN)

AF:

0.458

AC:

4841

AN:

10576

Middle Eastern (MID)

AF:

0.537

AC:

158

AN:

294

European-Non Finnish (NFE)

AF:

0.460

AC:

31251

AN:

67972

Other (OTH)

AF:

0.523

AC:

1102

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1939

3879

5818

7758

9697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.484

Hom.:

34869

Bravo

AF:

0.534

Asia WGS

AF:

0.620

AC:

2156

AN:

3478

EpiCase

AF:

0.462

EpiControl

AF:

0.464

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 27, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.1

(source)

DANN

Benign

0.91

PhyloP100

0.073

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs1063639

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over