rs736086

Variant names:

• chr10-74924027-A-G
• rs736086
• NM_012330.4:c.622-35943A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-74924027-A-G
• chr10-74924027-A-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.622-35943A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,992 control chromosomes in the GnomAD database, including 8,727 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 (8727 hom., cov: 32)
• Consequence: KAT6B NM_012330.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.572
• Publications: 1 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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT6B	NM_012330.4	c.622-35943A>G		intron_variant	Intron 3 of 17	ENST00000287239.10	NP_036462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT6B	ENST00000287239.10	c.622-35943A>G		intron_variant	Intron 3 of 17	1	NM_012330.4	ENSP00000287239.4

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38063 AN: 151874 Hom.: 8699 Cov.: 32

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.0402

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.251 AC: 38136 AN: 151992 Hom.: 8727 Cov.: 32 AF XY: 0.245 AC XY: 18200 AN XY: 74324

African (AFR) AF: 0.606 AC: 25064 AN: 41364

American (AMR) AF: 0.142 AC: 2173 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 402 AN: 3464

East Asian (EAS) AF: 0.192 AC: 993 AN: 5162

South Asian (SAS) AF: 0.328 AC: 1579 AN: 4818

European-Finnish (FIN) AF: 0.0402 AC: 427 AN: 10610

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6956 AN: 68002

Other (OTH) AF: 0.213 AC: 448 AN: 2108

Alfa AF: 0.121 Hom.: 1007

Bravo AF: 0.268

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.88
PhyloP100		0.57
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: rs736086; hg19: chr10-76683785;