rs3791373

chr2-239083142-A-G

Variant summary

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

The NM_001378414.1(HDAC4):c.2533-921T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 152,204 control chromosomes in the GnomAD database, including 11,463 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 0.38 (11463 hom., cov: 35)
• Consequence: HDAC4 NM_001378414.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.911

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 (AMR) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDAC4	NM_001378414.1	c.2533-921T>C		intron_variant		ENST00000543185.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC4	ENST00000543185.6	c.2533-921T>C		intron_variant		5	NM_001378414.1	A1
HDAC4	ENST00000345617.7	c.2518-921T>C		intron_variant		1		P4
HDAC4	ENST00000487617.5	n.425-921T>C		intron_variant, non_coding_transcript_variant		3
HDAC4	ENST00000690129.1	n.547-921T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57962 AN: 152086 Hom.: 11447 Cov.: 35

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.381 AC: 57996 AN: 152204 Hom.: 11463 Cov.: 35 AF XY: 0.384 AC XY: 28583 AN XY: 74404

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.378

Alfa AF: 0.396 Hom.: 4864

Bravo AF: 0.386

Asia WGS AF: 0.383 AC: 1328 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	0.56
Dann	Benign	0.26

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: rs3791373; hg19: chr2-240004838;