rs10200850

Variant names:

• chr2-239313206-G-A
• rs10200850
• NM_001378414.1:c.22+39472C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-239313206-G-A
• chr2-239313206-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.22+39472C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,238 control chromosomes in the GnomAD database, including 1,369 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 0.10 (1369 hom., cov: 32)
• Consequence: HDAC4 NM_001378414.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456
• Publications: 6 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378414.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC4	NM_001378414.1	MANE Select	c.22+39472C>T		intron	N/A	NP_001365343.1
	HDAC4	NM_001378415.1		c.22+39472C>T		intron	N/A	NP_001365344.1
	HDAC4	NM_001378416.1		c.22+39472C>T		intron	N/A	NP_001365345.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC4	ENST00000543185.6	TSL:5 MANE Select	c.22+39472C>T		intron	N/A	ENSP00000440481.3
	HDAC4	ENST00000345617.7	TSL:1	c.22+39472C>T		intron	N/A	ENSP00000264606.3
	HDAC4	ENST00000493582.5	TSL:1	n.494+39472C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15593 AN: 152120 Hom.: 1362 Cov.: 32

Gnomad AFR AF: 0.0820

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.0904

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.0645

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0662

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.103 AC: 15611 AN: 152238 Hom.: 1369 Cov.: 32 AF XY: 0.109 AC XY: 8095 AN XY: 74430

African (AFR) AF: 0.0819 AC: 3405 AN: 41556

American (AMR) AF: 0.193 AC: 2957 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0904 AC: 314 AN: 3472

East Asian (EAS) AF: 0.418 AC: 2157 AN: 5160

South Asian (SAS) AF: 0.265 AC: 1278 AN: 4824

European-Finnish (FIN) AF: 0.0645 AC: 684 AN: 10608

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0662 AC: 4501 AN: 68012

Other (OTH) AF: 0.105 AC: 222 AN: 2114

Alfa AF: 0.0829 Hom.: 404

Bravo AF: 0.107

Asia WGS AF: 0.331 AC: 1154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.77
DANN	Benign	0.82
PhyloP100		-0.46
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: rs10200850; hg19: chr2-240234901;