chr3-20119604-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003884.5(KAT2B):c.1157A>G(p.Asn386Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,613,994 control chromosomes in the GnomAD database, including 1,243 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 237 hom., cov: 32)

Exomes 𝑓: 0.013 ( 1006 hom. )

Consequence

KAT2B
NM_003884.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.302

Publications

21 publications found

Variant links:

Genes affected

KAT2B (HGNC:8638): (lysine acetyltransferase 2B) CBP and p300 are large nuclear proteins that bind to many sequence-specific factors involved in cell growth and/or differentiation, including c-jun and the adenoviral oncoprotein E1A. The protein encoded by this gene associates with p300/CBP. It has in vitro and in vivo binding activity with CBP and p300, and competes with E1A for binding sites in p300/CBP. It has histone acetyl transferase activity with core histones and nucleosome core particles, indicating that this protein plays a direct role in transcriptional regulation. [provided by RefSeq, Jul 2008]

KAT2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015796125).

BP6

Variant 3-20119604-A-G is Benign according to our data. Variant chr3-20119604-A-G is described in ClinVar as Benign. ClinVar VariationId is 1229746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT2B	NM_003884.5 link	c.1157A>G	p.Asn386Ser	missense_variant	Exon 8 of 18	ENST00000263754.5	NP_003875.3	Q92831
KAT2B	XM_005265528.5 link	c.1157A>G	p.Asn386Ser	missense_variant	Exon 8 of 17		XP_005265585.1
KAT2B	XM_047449147.1 link	c.866A>G	p.Asn289Ser	missense_variant	Exon 10 of 20		XP_047305103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT2B	ENST00000263754.5 link	c.1157A>G	p.Asn386Ser	missense_variant	Exon 8 of 18	1	NM_003884.5	ENSP00000263754.4		Q92831
KAT2B	ENST00000469085.1 link	n.147A>G		non_coding_transcript_exon_variant	Exon 3 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.0337

AC:

5125

AN:

152168

Hom.:

235

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0717

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0189

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.214

Gnomad SAS

AF:

0.0174

Gnomad FIN

AF:

0.0337

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00334

Gnomad OTH

AF:

0.0325

GnomAD2 exomes

AF:

0.0328

AC:

8171

AN:

249006

AF XY:

0.0291

show subpopulations

Gnomad AFR exome

AF:

0.0722

Gnomad AMR exome

AF:

0.0360

Gnomad ASJ exome

AF:

0.00228

Gnomad EAS exome

AF:

0.222

Gnomad FIN exome

AF:

0.0340

Gnomad NFE exome

AF:

0.00319

Gnomad OTH exome

AF:

0.0219

GnomAD4 exome

AF:

0.0125

AC:

18316

AN:

1461710

Hom.:

1006

Cov.:

AF XY:

0.0122

AC XY:

8842

AN XY:

727168

show subpopulations

African (AFR)

AF:

0.0741

AC:

2478

AN:

33458

American (AMR)

AF:

0.0341

AC:

1523

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00256

AC:

AN:

26136

East Asian (EAS)

AF:

0.192

AC:

7636

AN:

39690

South Asian (SAS)

AF:

0.0134

AC:

1154

AN:

86256

European-Finnish (FIN)

AF:

0.0314

AC:

1678

AN:

53408

Middle Eastern (MID)

AF:

0.0151

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00213

AC:

2368

AN:

1111906

Other (OTH)

AF:

0.0219

AC:

1325

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

811

1622

2434

3245

4056

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

278

556

834

1112

1390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0337

AC:

5136

AN:

152284

Hom.:

237

Cov.:

AF XY:

0.0354

AC XY:

2633

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.0718

AC:

2985

AN:

41566

American (AMR)

AF:

0.0188

AC:

288

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00403

AC:

AN:

3470

East Asian (EAS)

AF:

0.214

AC:

1105

AN:

5162

South Asian (SAS)

AF:

0.0172

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0337

AC:

358

AN:

10618

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00334

AC:

227

AN:

68030

Other (OTH)

AF:

0.0322

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

238

475

713

950

1188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0156

Hom.:

441

Bravo

AF:

0.0365

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.0649

AC:

286

ESP6500EA

AF:

0.00291

AC:

ExAC

AF:

0.0320

AC:

3883

Asia WGS

AF:

0.0970

AC:

336

AN:

3478

EpiCase

AF:

0.00311

EpiControl

AF:

0.00320

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.025

(source)

DANN

Benign

0.21

DEOGEN2

Benign

0.23

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.60

PhyloP100

-0.30

PrimateAI

Benign

0.29

PROVEAN

Benign

0.060

REVEL

Benign

0.17

Sift

Benign

0.92

Sift4G

Benign

0.85

Polyphen

0.0020

Vest4

0.020

MPC

0.35

ClinPred

0.0022

GERP RS

-12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.018

gMVP

0.12

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over