17-7846859-TACCACCACCACCACCACCACCACC-TACC

Variant summary

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

The NM_001348716.2(KDM6B):c.771_791del(p.Pro258_Pro264del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000111 in 1,215,894 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 0.000093 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00011 (0 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 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM6B	NM_001348716.2	c.771_791del	p.Pro258_Pro264del	inframe_deletion	10/24	ENST00000448097.7
KDM6B	NM_001080424.2	c.771_791del	p.Pro258_Pro264del	inframe_deletion	9/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM6B	ENST00000448097.7	c.771_791del	p.Pro258_Pro264del	inframe_deletion	10/24	5	NM_001348716.2	A2
KDM6B	ENST00000254846.9	c.771_791del	p.Pro258_Pro264del	inframe_deletion	9/22	1		P2
KDM6B	ENST00000570632.1	c.711+138_711+158del		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0000930 AC: 11 AN: 118290 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000691

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000857

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: 0.000113 AC: 124 AN: 1097542 Hom.: 0 AF XY: 0.000101 AC XY: 56 AN XY: 554650

Gnomad4 AFR exome AF: 0.0000782

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000397

Gnomad4 FIN exome AF: 0.0000278

Gnomad4 NFE exome AF: 0.000140

Gnomad4 OTH exome AF: 0.0000626

GnomAD4 genome AF: 0.0000929 AC: 11 AN: 118352 Hom.: 0 Cov.: 0 AF XY: 0.000108 AC XY: 6 AN XY: 55510

Gnomad4 AFR AF: 0.0000689

Gnomad4 AMR AF: 0.0000856

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

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;