17-7846859-T-TACCACCACCACC

Variant names:

• chr17-7846859-T-TACCACCACCACC
• rs61462443
• NM_001348716.2:c.780_791dupACCACCACCACC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001348716.2(KDM6B):​c.780_791dupACCACCACCACC​(p.Pro261_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 0.00188 in 1,097,236 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0019 (9 hom.)
  • Failed GnomAD Quality Control
• Consequence: KDM6B NM_001348716.2 disruptive_inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.250

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 17-7846859-T-TACCACCACCACC is Benign according to our data. Variant chr17-7846859-T-TACCACCACCACC is described in ClinVar as [Likely_benign]. Clinvar id is 3037897.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.00188 (2062/1097236) while in subpopulation EAS AF = 0.00907 (323/35624). AF 95% confidence interval is 0.00825. There are 9 homozygotes in GnomAdExome4. There are 1009 alleles in the male GnomAdExome4 subpopulation. Median coverage is 43. This position FAILED quality control check.
• BS2: High AC in GnomAdExome4 at 2062 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM6B	NM_001348716.2	c.780_791dupACCACCACCACC	p.Pro261_Pro264dup	disruptive_inframe_insertion	Exon 10 of 24	ENST00000448097.7	NP_001335645.1
KDM6B	NM_001080424.2	c.780_791dupACCACCACCACC	p.Pro261_Pro264dup	disruptive_inframe_insertion	Exon 9 of 22		NP_001073893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM6B	ENST00000448097.7	c.780_791dupACCACCACCACC	p.Pro261_Pro264dup	disruptive_inframe_insertion	Exon 10 of 24	5	NM_001348716.2	ENSP00000412513.2
KDM6B	ENST00000254846.9	c.780_791dupACCACCACCACC	p.Pro261_Pro264dup	disruptive_inframe_insertion	Exon 9 of 22	1		ENSP00000254846.5
KDM6B	ENST00000570632.1	c.711+147_711+158dupACCACCACCACC		intron_variant	Intron 7 of 8	5		ENSP00000458445.1

Frequencies

GnomAD3 genomes AF: 0.00229 AC: 271 AN: 118286 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00311

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00214

Gnomad ASJ AF: 0.00481

Gnomad EAS AF: 0.00787

Gnomad SAS AF: 0.000831

Gnomad FIN AF: 0.00116

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00167

Gnomad OTH AF: 0.000661

GnomAD4 exome AF: 0.00188 AC: 2062 AN: 1097236 Hom.: 9 Cov.: 43 AF XY: 0.00182 AC XY: 1009 AN XY: 554504

Gnomad4 AFR exome AF: 0.00313 AC: 80 AN: 25578

Gnomad4 AMR exome AF: 0.00171 AC: 66 AN: 38600

Gnomad4 ASJ exome AF: 0.00407 AC: 91 AN: 22352

Gnomad4 EAS exome AF: 0.00907 AC: 323 AN: 35624

Gnomad4 SAS exome AF: 0.00118 AC: 89 AN: 75528

Gnomad4 FIN exome AF: 0.00103 AC: 37 AN: 35930

Gnomad4 NFE exome AF: 0.00157 AC: 1271 AN: 812110

Gnomad4 Remaining exome AF: 0.00209 AC: 100 AN: 47948

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00230 AC: 272 AN: 118348 Hom.: 1 Cov.: 0 AF XY: 0.00211 AC XY: 117 AN XY: 55506

Gnomad4 AFR AF: 0.00314 AC: 0.00313642 AN: 0.00313642

Gnomad4 AMR AF: 0.00214 AC: 0.00214004 AN: 0.00214004

Gnomad4 ASJ AF: 0.00481 AC: 0.00481078 AN: 0.00481078

Gnomad4 EAS AF: 0.00789 AC: 0.00789474 AN: 0.00789474

Gnomad4 SAS AF: 0.000835 AC: 0.000834725 AN: 0.000834725

Gnomad4 FIN AF: 0.00116 AC: 0.00115971 AN: 0.00115971

Gnomad4 NFE AF: 0.00167 AC: 0.0016677 AN: 0.0016677

Gnomad4 OTH AF: 0.000654 AC: 0.00065445 AN: 0.00065445

Alfa AF: 0.00 Hom.: 2265

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

KDM6B-related disorder Benign:1

Oct 07, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KDM6B: BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=89/11	polymorphism

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;