rs1868627

Variant names:

• chr10-74960323-C-T
• rs1868627
• NM_012330.4:c.730+245C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012330.4(KAT6B):​c.730+245C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 151,890 control chromosomes in the GnomAD database, including 1,835 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (1835 hom., cov: 32)
• Consequence: KAT6B NM_012330.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.42
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-74960323-C-T is Benign according to our data. Variant chr10-74960323-C-T is described in ClinVar as Benign. ClinVar VariationId is 561581.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 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.730+245C>T		intron	N/A	NP_036462.2
	KAT6B	NM_001370136.1		c.730+245C>T		intron	N/A	NP_001357065.1
	KAT6B	NM_001370137.1		c.730+245C>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.730+245C>T		intron	N/A	ENSP00000287239.4
	KAT6B	ENST00000372711.2	TSL:1	c.730+245C>T		intron	N/A	ENSP00000361796.1
	KAT6B	ENST00000649442.1		c.*195C>T		3_prime_UTR	Exon 4 of 4	ENSP00000498102.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18826 AN: 151774 Hom.: 1834 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0738

Gnomad ASJ AF: 0.0813

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.0337

Gnomad MID AF: 0.0801

Gnomad NFE AF: 0.0661

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.124 AC: 18833 AN: 151890 Hom.: 1835 Cov.: 32 AF XY: 0.124 AC XY: 9207 AN XY: 74242

African (AFR) AF: 0.254 AC: 10521 AN: 41398

American (AMR) AF: 0.0737 AC: 1125 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0813 AC: 282 AN: 3470

East Asian (EAS) AF: 0.0998 AC: 516 AN: 5168

South Asian (SAS) AF: 0.270 AC: 1300 AN: 4818

European-Finnish (FIN) AF: 0.0337 AC: 354 AN: 10490

Middle Eastern (MID) AF: 0.0793 AC: 23 AN: 290

European-Non Finnish (NFE) AF: 0.0660 AC: 4489 AN: 67964

Other (OTH) AF: 0.105 AC: 222 AN: 2114

Alfa AF: 0.0936 Hom.: 127

Bravo AF: 0.127

Asia WGS AF: 0.178 AC: 619 AN: 3470

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.46
PhyloP100		-1.4
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: rs1868627; hg19: chr10-76720081;