2-239164099-A-C

Position:

• chr2-239164099-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001378414.1(HDAC4):​c.491-176T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 151,940 control chromosomes in the GnomAD database, including 29,608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.62 (29608 hom., cov: 31)
• Consequence: HDAC4 NM_001378414.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00600

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-239164099-A-C is Benign according to our data. Variant chr2-239164099-A-C is described in ClinVar as [Benign]. Clinvar id is 1246960.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDAC4	NM_001378414.1	c.491-176T>G		intron_variant		ENST00000543185.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC4	ENST00000543185.6	c.491-176T>G		intron_variant		5	NM_001378414.1	A1

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93644 AN: 151820 Hom.: 29596 Cov.: 31

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.617 AC: 93686 AN: 151940 Hom.: 29608 Cov.: 31 AF XY: 0.618 AC XY: 45863 AN XY: 74248

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.596

Alfa AF: 0.664 Hom.: 40578

Bravo AF: 0.589

Asia WGS AF: 0.614 AC: 2137 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2290089; hg19: chr2-240085795;