rs3791398

chr2-239103970-G-A

Variant summary

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

The NM_001378414.1(HDAC4):c.2113-1074C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,228 control chromosomes in the GnomAD database, including 6,283 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 0.28 (6283 hom., cov: 34)
• Consequence: HDAC4 NM_001378414.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDAC4	NM_001378414.1	c.2113-1074C>T		intron_variant		ENST00000543185.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC4	ENST00000543185.6	c.2113-1074C>T		intron_variant		5	NM_001378414.1	A1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42827 AN: 152110 Hom.: 6276 Cov.: 34

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.282 AC: 42874 AN: 152228 Hom.: 6283 Cov.: 34 AF XY: 0.283 AC XY: 21093 AN XY: 74420

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.298

Alfa AF: 0.310 Hom.: 6504

Bravo AF: 0.275

Asia WGS AF: 0.246 AC: 860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	2.1
Dann	Benign	0.41

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: rs3791398; hg19: chr2-240025666;