Variant 17-7846859-TACCACCACCACCACCACCACCACC-TACCACCACCACCACCACCACCACCACCACCACCACCACCACCACC 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.771_791dupACCACCACCACCACCACCACC(p.Pro258_Pro264dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000292 in 1,097,534 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000051 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000029 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KDM6B
NM_001348716.2 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.250

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BS2

High AC in GnomAdExome4 at 32 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/exons	MANE	Protein	UniProt
KDM6B	NM_001348716.2 link	c.771_791dupACCACCACCACCACCACCACC	p.Pro258_Pro264dup	disruptive_inframe_insertion	10/24	ENST00000448097.7	NP_001335645.1
KDM6B	NM_001080424.2 link	c.771_791dupACCACCACCACCACCACCACC	p.Pro258_Pro264dup	disruptive_inframe_insertion	9/22		NP_001073893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KDM6B	ENST00000448097.7 link	c.771_791dupACCACCACCACCACCACCACC	p.Pro258_Pro264dup	disruptive_inframe_insertion	10/24	5	NM_001348716.2	ENSP00000412513.2	O15054-2
KDM6B	ENST00000254846.9 link	c.771_791dupACCACCACCACCACCACCACC	p.Pro258_Pro264dup	disruptive_inframe_insertion	9/22	1		ENSP00000254846.5	O15054-1
KDM6B	ENST00000570632.1 link	c.711+138_711+158dupACCACCACCACCACCACCACC		intron_variant		5		ENSP00000458445.1	I3L0Z0

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

118294

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000691

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000277

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000516

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000292

AC:

AN:

1097534

Hom.:

Cov.:

AF XY:

0.0000415

AC XY:

AN XY:

554644

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000777

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000281

Gnomad4 SAS exome

AF:

0.000146

Gnomad4 FIN exome

AF:

0.0000278

Gnomad4 NFE exome

AF:

0.0000160

Gnomad4 OTH exome

AF:

0.0000626

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000507

AC:

AN:

118356

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

55512

show subpopulations

Gnomad4 AFR

AF:

0.0000689

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000278

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000516

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over