10-74905078-C-T

Variant names:

• chr10-74905078-C-T
• rs2001245
• NM_012330.4:c.622-54892C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012330.4(KAT6B):​c.622-54892C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,078 control chromosomes in the GnomAD database, including 15,754 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 0.40 (15754 hom., cov: 32)
• Consequence: KAT6B NM_012330.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.476
• Publications: 3 publications found

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]

KAT6B Gene-Disease associations (from GenCC):

• blepharophimosis - intellectual disability syndrome, SBBYS type

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• genitopatellar syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• KAT6B-related multiple congenital anomalies syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• RASopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012330.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAT6B	NM_012330.4	MANE Select	c.622-54892C>T		intron	N/A	NP_036462.2
	KAT6B	NM_001370136.1		c.622-54892C>T		intron	N/A	NP_001357065.1
	KAT6B	NM_001370137.1		c.622-54892C>T		intron	N/A	NP_001357066.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAT6B	ENST00000287239.10	TSL:1 MANE Select	c.622-54892C>T		intron	N/A	ENSP00000287239.4
	KAT6B	ENST00000372711.2	TSL:1	c.622-54892C>T		intron	N/A	ENSP00000361796.1
	KAT6B	ENST00000648725.1		c.622-54892C>T		intron	N/A	ENSP00000497841.1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 61010 AN: 151960 Hom.: 15752 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.0511

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.401 AC: 61000 AN: 152078 Hom.: 15754 Cov.: 32 AF XY: 0.396 AC XY: 29471 AN XY: 74342

African (AFR) AF: 0.119 AC: 4952 AN: 41498

American (AMR) AF: 0.374 AC: 5714 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2060 AN: 3470

East Asian (EAS) AF: 0.0514 AC: 266 AN: 5178

South Asian (SAS) AF: 0.230 AC: 1105 AN: 4808

European-Finnish (FIN) AF: 0.555 AC: 5856 AN: 10558

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39349 AN: 67970

Other (OTH) AF: 0.430 AC: 908 AN: 2110

Alfa AF: 0.465 Hom.: 19263

Bravo AF: 0.377

Asia WGS AF: 0.127 AC: 447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.25
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2001245; hg19: chr10-76664836;