Variant 17-7846859-TACCACCACCACCACCACCACCACC-TACCACC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_001348716.2(KDM6B):c.774_791delACCACCACCACCACCACC(p.Pro259_Pro264del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000126 in 1,215,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

KDM6B
NM_001348716.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67

Variant links:

Genes affected

KDM6B (HGNC:29012): (lysine demethylase 6B) The protein encoded by this gene is a lysine-specific demethylase that specifically demethylates di- or tri-methylated lysine 27 of histone H3 (H3K27me2 or H3K27me3). H3K27 trimethylation is a repressive epigenetic mark controlling chromatin organization and gene silencing. This protein can also demethylate non-histone proteins such as retinoblastoma protein. Through its demethylation actvity this gene influences cellular differentiation and development, tumorigenesis, inflammatory diseases, and neurodegenerative diseases. This protein has two classical nuclear localization signals at its N-terminus. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2017]

KDM6B links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BS2

High AC in GnomAd4 at 15 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM6B	NM_001348716.2 link	c.774_791delACCACCACCACCACCACC	p.Pro259_Pro264del	disruptive_inframe_deletion	Exon 10 of 24	ENST00000448097.7	NP_001335645.1
KDM6B	NM_001080424.2 link	c.774_791delACCACCACCACCACCACC	p.Pro259_Pro264del	disruptive_inframe_deletion	Exon 9 of 22		NP_001073893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KDM6B	ENST00000448097.7 link	c.774_791delACCACCACCACCACCACC	p.Pro259_Pro264del	disruptive_inframe_deletion	Exon 10 of 24	5	NM_001348716.2	ENSP00000412513.2	O15054-2
KDM6B	ENST00000254846.9 link	c.774_791delACCACCACCACCACCACC	p.Pro259_Pro264del	disruptive_inframe_deletion	Exon 9 of 22	1		ENSP00000254846.5	O15054-1
KDM6B	ENST00000570632.1 link	c.711+141_711+158delACCACCACCACCACCACC		intron_variant	Intron 7 of 8	5		ENSP00000458445.1	I3L0Z0

Frequencies

GnomAD3 genomes

AF:

0.000127

AC:

AN:

118292

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000257

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000238

Gnomad SAS

AF:

0.000277

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000126

AC:

138

AN:

1097536

Hom.:

AF XY:

0.000139

AC XY:

AN XY:

554648

show subpopulations

Gnomad4 AFR exome

AF:

0.0000782

Gnomad4 AMR exome

AF:

0.000311

Gnomad4 ASJ exome

AF:

0.0000895

Gnomad4 EAS exome

AF:

0.000168

Gnomad4 SAS exome

AF:

0.000318

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000108

Gnomad4 OTH exome

AF:

0.0000834

GnomAD4 genome

AF:

0.000127

AC:

AN:

118354

Hom.:

Cov.:

AF XY:

0.0000901

AC XY:

AN XY:

55510

show subpopulations

Gnomad4 AFR

AF:

0.000138

Gnomad4 AMR

AF:

0.000257

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000239

Gnomad4 SAS

AF:

0.000278

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

KDM6B-related disorder

Uncertain:1

Oct 13, 2022

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The KDM6B c.774_791del18 variant is predicted to result in an in-frame deletion (p.Pro259_Pro264del). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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