17-7846859-TACCACCACCACCACCACCACCACC-TACCACCACCACC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001348716.2(KDM6B):c.780_791del(p.Pro261_Pro264del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000995 in 1,215,676 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00010 (1 hom.)
• Consequence: KDM6B NM_001348716.2 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM6B	NM_001348716.2	c.780_791del	p.Pro261_Pro264del	inframe_deletion	10/24	ENST00000448097.7
KDM6B	NM_001080424.2	c.780_791del	p.Pro261_Pro264del	inframe_deletion	9/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM6B	ENST00000448097.7	c.780_791del	p.Pro261_Pro264del	inframe_deletion	10/24	5	NM_001348716.2	A2
KDM6B	ENST00000254846.9	c.780_791del	p.Pro261_Pro264del	inframe_deletion	9/22	1		P2
KDM6B	ENST00000570632.1	c.711+147_711+158del		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 7 AN: 118288 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000238

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000516

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000104 AC: 114 AN: 1097388 Hom.: 1 AF XY: 0.000106 AC XY: 59 AN XY: 554582

Gnomad4 AFR exome AF: 0.0000391

Gnomad4 AMR exome AF: 0.0000777

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000225

Gnomad4 SAS exome AF: 0.000106

Gnomad4 FIN exome AF: 0.000139

Gnomad4 NFE exome AF: 0.000106

Gnomad4 OTH exome AF: 0.0000209

GnomAD4 genome AF: 0.0000592 AC: 7 AN: 118288 Hom.: 0 Cov.: 0 AF XY: 0.0000722 AC XY: 4 AN XY: 55438

Gnomad4 AFR AF: 0.000104

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000238

Gnomad4 SAS AF: 0.00

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs61462443; hg19: chr17-7750177;