dbSNP rs7899137: KAT6B:c.622-51266A>C (chr10-74908704-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012330.4(KAT6B):c.622-51266A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 152,096 control chromosomes in the GnomAD database, including 15,954 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 ( 15954 hom., cov: 32)

Consequence

KAT6B
NM_012330.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0540

Publications

5 publications found

Variant links:

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

KAT6B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT6B	NM_012330.4 link	c.622-51266A>C		intron_variant	Intron 3 of 17	ENST00000287239.10	NP_036462.2	Q8WYB5-1B2RWN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT6B	ENST00000287239.10 link	c.622-51266A>C		intron_variant	Intron 3 of 17	1	NM_012330.4	ENSP00000287239.4		Q8WYB5-1

Frequencies

GnomAD3 genomes

AF:

0.404

AC:

61357

AN:

151978

Hom.:

15952

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.734

Gnomad AMR

AF:

0.376

Gnomad ASJ

AF:

0.594

Gnomad EAS

AF:

0.0510

Gnomad SAS

AF:

0.229

Gnomad FIN

AF:

0.555

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.437

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

GnomAD4 genome

AF:

0.403

AC:

61346

AN:

152096

Hom.:

15954

Cov.:

AF XY:

0.398

AC XY:

29626

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.120

AC:

4966

AN:

41512

American (AMR)

AF:

0.375

AC:

5731

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.594

AC:

2061

AN:

3470

East Asian (EAS)

AF:

0.0513

AC:

266

AN:

5184

South Asian (SAS)

AF:

0.230

AC:

1110

AN:

4824

European-Finnish (FIN)

AF:

0.555

AC:

5863

AN:

10570

Middle Eastern (MID)

AF:

0.412

AC:

121

AN:

294

European-Non Finnish (NFE)

AF:

0.584

AC:

39650

AN:

67950

Other (OTH)

AF:

0.431

AC:

910

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1533

3066

4598

6131

7664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

540

1080

1620

2160

2700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.528

Hom.:

56710

Bravo

AF:

0.379

Asia WGS

AF:

0.129

AC:

452

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.5

(source)

DANN

Benign

0.47

PhyloP100

-0.054

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over