Variant 2-239052959-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.*138C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00947 in 999,266 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0082 ( 16 hom., cov: 33)

Exomes 𝑓: 0.0097 ( 56 hom. )

Consequence

HDAC4
NM_001378414.1 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.257

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 2-239052959-G-A is Benign according to our data. Variant chr2-239052959-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1214616.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00823 (1254/152362) while in subpopulation NFE AF= 0.0127 (867/68038). AF 95% confidence interval is 0.012. There are 16 homozygotes in gnomad4. There are 614 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1254 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDAC4	NM_001378414.1 linkuse as main transcript	c.*138C>T		3_prime_UTR_variant	27/27	ENST00000543185.6

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC4	ENST00000543185.6 linkuse as main transcript	c.*138C>T	3_prime_UTR_variant	27/27	5	NM_001378414.1	A1
HDAC4	ENST00000345617.7 linkuse as main transcript	c.*138C>T	3_prime_UTR_variant	27/27	1		P4	P56524-1
HDAC4	ENST00000690129.1 linkuse as main transcript	n.1422C>T	non_coding_transcript_exon_variant	10/10

Frequencies

GnomAD3 genomes

AF:

0.00824

AC:

1254

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0209

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.00478

GnomAD4 exome

AF:

0.00970

AC:

8211

AN:

846904

Hom.:

Cov.:

AF XY:

0.00939

AC XY:

4175

AN XY:

444480

show subpopulations

Gnomad4 AFR exome

AF:

0.00121

Gnomad4 AMR exome

AF:

0.00217

Gnomad4 ASJ exome

AF:

0.0173

Gnomad4 EAS exome

AF:

0.0000550

Gnomad4 SAS exome

AF:

0.00226

Gnomad4 FIN exome

AF:

0.0214

Gnomad4 NFE exome

AF:

0.0110

Gnomad4 OTH exome

AF:

0.00886

GnomAD4 genome

AF:

0.00823

AC:

1254

AN:

152362

Hom.:

Cov.:

AF XY:

0.00824

AC XY:

614

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.00189

Gnomad4 ASJ

AF:

0.0167

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0209

Gnomad4 NFE

AF:

0.0127

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.0148

Hom.:

Bravo

AF:

0.00587

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.1

DANN

Benign

0.90

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