Variant rs72630048 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_018486.3(HDAC8):c.438-15C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0535 in 1,122,577 control chromosomes in the GnomAD database, including 9,177 homozygotes. There are 20,953 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 849 hom., 2353 hem., cov: 22)

Exomes 𝑓: 0.052 ( 8328 hom. 18600 hem. )

Consequence

HDAC8
NM_018486.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.79

Variant links:

Genes affected

HDAC8 (HGNC:13315): (histone deacetylase 8) 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 I of the histone deacetylase family. It catalyzes the deacetylation of lysine residues in the histone N-terminal tails and represses transcription in large multiprotein complexes with transcriptional co-repressors. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

HDAC8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant X-72495283-G-A is Benign according to our data. Variant chrX-72495283-G-A is described in ClinVar as [Benign]. Clinvar id is 158662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDAC8	NM_018486.3 linkuse as main transcript	c.438-15C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000373573.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC8	ENST00000373573.9 linkuse as main transcript	c.438-15C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_018486.3	P4	Q9BY41-1

Frequencies

GnomAD3 genomes

AF:

0.0636

AC:

7076

AN:

111199

Hom.:

854

Cov.:

AF XY:

0.0704

AC XY:

2353

AN XY:

33435

show subpopulations

Gnomad AFR

AF:

0.0498

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.0352

Gnomad EAS

AF:

0.725

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.0281

Gnomad MID

AF:

0.00844

Gnomad NFE

AF:

0.00500

Gnomad OTH

AF:

0.0670

GnomAD3 exomes

AF:

0.141

AC:

23113

AN:

164484

Hom.:

3981

AF XY:

0.128

AC XY:

6655

AN XY:

52048

show subpopulations

Gnomad AFR exome

AF:

0.0504

Gnomad AMR exome

AF:

0.335

Gnomad ASJ exome

AF:

0.0299

Gnomad EAS exome

AF:

0.736

Gnomad SAS exome

AF:

0.204

Gnomad FIN exome

AF:

0.0313

Gnomad NFE exome

AF:

0.00540

Gnomad OTH exome

AF:

0.0908

GnomAD4 exome

AF:

0.0524

AC:

52968

AN:

1011326

Hom.:

8328

Cov.:

AF XY:

0.0636

AC XY:

18600

AN XY:

292506

show subpopulations

Gnomad4 AFR exome

AF:

0.0496

Gnomad4 AMR exome

AF:

0.315

Gnomad4 ASJ exome

AF:

0.0322

Gnomad4 EAS exome

AF:

0.770

Gnomad4 SAS exome

AF:

0.209

Gnomad4 FIN exome

AF:

0.0313

Gnomad4 NFE exome

AF:

0.00355

Gnomad4 OTH exome

AF:

0.0692

GnomAD4 genome

AF:

0.0636

AC:

7077

AN:

111251

Hom.:

849

Cov.:

AF XY:

0.0702

AC XY:

2353

AN XY:

33497

show subpopulations

Gnomad4 AFR

AF:

0.0498

Gnomad4 AMR

AF:

0.177

Gnomad4 ASJ

AF:

0.0352

Gnomad4 EAS

AF:

0.725

Gnomad4 SAS

AF:

0.217

Gnomad4 FIN

AF:

0.0281

Gnomad4 NFE

AF:

0.00500

Gnomad4 OTH

AF:

0.0702

Alfa

AF:

0.0316

Hom.:

1547

Bravo

AF:

0.0847

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 22, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Cornelia de Lange syndrome 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over