Variant 2-239053442-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001378414.1(HDAC4):c.3230+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,610,110 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 5 hom. )

Consequence

HDAC4
NM_001378414.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.178

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 2-239053442-G-A is Benign according to our data. Variant chr2-239053442-G-A is described in ClinVar as [Benign]. Clinvar id is 2887533.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00109 (166/152326) while in subpopulation NFE AF= 0.00193 (131/68024). AF 95% confidence interval is 0.00166. There are 0 homozygotes in gnomad4. There are 74 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 166 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDAC4	NM_001378414.1 linkuse as main transcript	c.3230+18C>T		intron_variant		ENST00000543185.6	NP_001365343.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
HDAC4	ENST00000543185.6 linkuse as main transcript	c.3230+18C>T	intron_variant	5	NM_001378414.1	ENSP00000440481	A1
HDAC4	ENST00000345617.7 linkuse as main transcript	c.3215+18C>T	intron_variant	1		ENSP00000264606	P4	P56524-1
HDAC4	ENST00000430200.1 linkuse as main transcript	c.487+18C>T	intron_variant	3		ENSP00000410551
HDAC4	ENST00000690129.1 linkuse as main transcript	n.1244+18C>T	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00109

AC:

166

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00193

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00110

AC:

272

AN:

248274

Hom.:

AF XY:

0.000974

AC XY:

131

AN XY:

134444

show subpopulations

Gnomad AFR exome

AF:

0.000872

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.000807

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000659

Gnomad FIN exome

AF:

0.000749

Gnomad NFE exome

AF:

0.00195

Gnomad OTH exome

AF:

0.000827

GnomAD4 exome

AF:

0.00172

AC:

2503

AN:

1457784

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

1168

AN XY:

724678

show subpopulations

Gnomad4 AFR exome

AF:

0.000718

Gnomad4 AMR exome

AF:

0.000292

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0000349

Gnomad4 FIN exome

AF:

0.000761

Gnomad4 NFE exome

AF:

0.00209

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.00109

AC:

166

AN:

152326

Hom.:

Cov.:

AF XY:

0.000994

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.00193

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00133

Hom.:

Bravo

AF:

0.00107

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 09, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.29

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over