2-239340592-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378414.1(HDAC4):c.22+12086A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 152,092 control chromosomes in the GnomAD database, including 31,763 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 0.65 (31763 hom., cov: 32)
• Consequence: HDAC4 NM_001378414.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDAC4	NM_001378414.1	c.22+12086A>G		intron_variant		ENST00000543185.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC4	ENST00000543185.6	c.22+12086A>G		intron_variant		5	NM_001378414.1	A1
HDAC4	ENST00000345617.7	c.22+12086A>G		intron_variant		1		P4
HDAC4	ENST00000493582.5	n.494+12086A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97994 AN: 151974 Hom.: 31708 Cov.: 32

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.628

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.645 AC: 98107 AN: 152092 Hom.: 31763 Cov.: 32 AF XY: 0.644 AC XY: 47887 AN XY: 74342

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.674

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.633

Alfa AF: 0.630 Hom.: 41129

Bravo AF: 0.638

Asia WGS AF: 0.690 AC: 2398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.55
Dann	Benign	0.27

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

Other links and lift over

dbSNP: rs908265; hg19: chr2-240262287;