chr2-239053235-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001378414.1(HDAC4):c.3231-99G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00564 in 1,491,208 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0060 ( 12 hom., cov: 33)
Exomes 𝑓: 0.0056 ( 39 hom. )
Consequence
HDAC4
NM_001378414.1 intron
NM_001378414.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.491
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]
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=-0.98).
BP6
?
Variant 2-239053235-C-T is Benign according to our data. Variant chr2-239053235-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1208308.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00596 (908/152310) while in subpopulation AMR AF= 0.00634 (97/15304). AF 95% confidence interval is 0.00532. There are 12 homozygotes in gnomad4. There are 546 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 909 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HDAC4 | NM_001378414.1 | c.3231-99G>A | intron_variant | ENST00000543185.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HDAC4 | ENST00000543185.6 | c.3231-99G>A | intron_variant | 5 | NM_001378414.1 | A1 | |||
HDAC4 | ENST00000345617.7 | c.3216-99G>A | intron_variant | 1 | P4 | ||||
HDAC4 | ENST00000430200.1 | c.488-99G>A | intron_variant | 3 | |||||
HDAC4 | ENST00000690129.1 | n.1245-99G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00597 AC: 909AN: 152192Hom.: 12 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
909
AN:
152192
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00560 AC: 7500AN: 1338898Hom.: 39 AF XY: 0.00555 AC XY: 3706AN XY: 668272
GnomAD4 exome
AF:
AC:
7500
AN:
1338898
Hom.:
AF XY:
AC XY:
3706
AN XY:
668272
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00596 AC: 908AN: 152310Hom.: 12 Cov.: 33 AF XY: 0.00733 AC XY: 546AN XY: 74474
GnomAD4 genome
?
AF:
AC:
908
AN:
152310
Hom.:
Cov.:
33
AF XY:
AC XY:
546
AN XY:
74474
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
2
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 | Feb 21, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at