rs4746248

Positions:

• chr10-74946123-G-A
• chr10-74946123-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012330.4(KAT6B):​c.622-13847G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,044 control chromosomes in the GnomAD database, including 8,368 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (8368 hom., cov: 32)
• Consequence: KAT6B NM_012330.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAT6B	NM_012330.4	c.622-13847G>A		intron_variant		ENST00000287239.10	NP_036462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAT6B	ENST00000287239.10	c.622-13847G>A		intron_variant		1	NM_012330.4	ENSP00000287239	P2

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37485 AN: 151926 Hom.: 8340 Cov.: 32

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.0405

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.213

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.247 AC: 37559 AN: 152044 Hom.: 8368 Cov.: 32 AF XY: 0.241 AC XY: 17952 AN XY: 74348

Gnomad4 AFR AF: 0.591

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.0405

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.211

Alfa AF: 0.116 Hom.: 2936

Bravo AF: 0.263

Asia WGS AF: 0.263 AC: 912 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.87
DANN	Benign	0.41

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: rs4746248; hg19: chr10-76705881;