10-74842497-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_012330.4(KAT6B):c.-258-101del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 519,738 control chromosomes in the GnomAD database, including 21,386 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (12529 hom., cov: 25)
  • Exomes 𝑓: 0.17 (8857 hom.)
• Consequence: KAT6B NM_012330.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.663

Genes affected

KAT6B (HGNC:17582): (lysine acetyltransferase 6B) The protein encoded by this gene is a histone acetyltransferase and component of the MOZ/MORF protein complex. In addition to its acetyltransferase activity, the encoded protein has transcriptional activation activity in its N-terminal end and transcriptional repression activity in its C-terminal end. This protein is necessary for RUNX2-dependent transcriptional activation and could be involved in brain development. Mutations have been found in patients with genitopatellar syndrome. A translocation of this gene and the CREBBP gene results in acute myeloid leukemias. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 10-74842497-CT-C is Benign according to our data. Variant chr10-74842497-CT-C is described in ClinVar as [Benign]. Clinvar id is 1237197.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KAT6B	NM_012330.4	c.-258-101del		intron_variant		ENST00000287239.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KAT6B	ENST00000287239.10	c.-258-101del		intron_variant		1	NM_012330.4	P2

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46378 AN: 151944 Hom.: 12485 Cov.: 25

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.0513

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.170 AC: 62549 AN: 367676 Hom.: 8857 AF XY: 0.175 AC XY: 33359 AN XY: 190120

Gnomad4 AFR exome AF: 0.704

Gnomad4 AMR exome AF: 0.289

Gnomad4 ASJ exome AF: 0.137

Gnomad4 EAS exome AF: 0.336

Gnomad4 SAS exome AF: 0.387

Gnomad4 FIN exome AF: 0.0536

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.306 AC: 46474 AN: 152062 Hom.: 12529 Cov.: 25 AF XY: 0.303 AC XY: 22528 AN XY: 74368

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.0513

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.267

Alfa AF: 0.212 Hom.: 887

Bravo AF: 0.334

Asia WGS AF: 0.386 AC: 1338 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 22, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs55787052; hg19: chr10-76602255;