rs7584828

Variant names:

• chr2-239258492-G-A
• rs7584828
• NM_001378414.1:c.23-21828C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-239258492-G-A
• chr2-239258492-G-C
• chr2-239258492-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378414.1(HDAC4):​c.23-21828C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,110 control chromosomes in the GnomAD database, including 6,549 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 0.25 (6549 hom., cov: 32)
• Consequence: HDAC4 NM_001378414.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with central hypotonia and dysmorphic facies

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• 2q37 microdeletion syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC4	NM_001378414.1	c.23-21828C>T		intron_variant	Intron 2 of 26	ENST00000543185.6	NP_001365343.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC4	ENST00000543185.6	c.23-21828C>T		intron_variant	Intron 2 of 26	5	NM_001378414.1	ENSP00000440481.3

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38330 AN: 151992 Hom.: 6527 Cov.: 32

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.252 AC: 38403 AN: 152110 Hom.: 6549 Cov.: 32 AF XY: 0.252 AC XY: 18702 AN XY: 74354

African (AFR) AF: 0.452 AC: 18721 AN: 41446

American (AMR) AF: 0.289 AC: 4417 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 563 AN: 3468

East Asian (EAS) AF: 0.474 AC: 2451 AN: 5174

South Asian (SAS) AF: 0.223 AC: 1077 AN: 4826

European-Finnish (FIN) AF: 0.103 AC: 1092 AN: 10600

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9364 AN: 67994

Other (OTH) AF: 0.239 AC: 506 AN: 2114

Alfa AF: 0.202 Hom.: 549

Bravo AF: 0.277

Asia WGS AF: 0.361 AC: 1253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.44
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7584828; hg19: chr2-240180188;