3-20095467-A-G

Variant names:

• chr3-20095467-A-G
• rs12636856
• NM_003884.5:c.576+59A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003884.5(KAT2B):​c.576+59A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0904 in 1,232,466 control chromosomes in the GnomAD database, including 7,829 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1293 hom., cov: 33)
  • Exomes 𝑓: 0.088 (6536 hom.)
• Consequence: KAT2B NM_003884.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.12

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-20095467-A-G is Benign according to our data. Variant chr3-20095467-A-G is described in ClinVar as [Benign]. Clinvar id is 1248240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT2B	NM_003884.5	c.576+59A>G		intron_variant	Intron 3 of 17	ENST00000263754.5	NP_003875.3
KAT2B	XM_005265528.5	c.576+59A>G		intron_variant	Intron 3 of 16		XP_005265585.1
KAT2B	XM_047449147.1	c.285+59A>G		intron_variant	Intron 5 of 19		XP_047305103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT2B	ENST00000263754.5	c.576+59A>G		intron_variant	Intron 3 of 17	1	NM_003884.5	ENSP00000263754.4
KAT2B	ENST00000426228.1	n.356+59A>G		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16653 AN: 152116 Hom.: 1289 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0634

Gnomad ASJ AF: 0.0939

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0703

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.0877 AC: 94769 AN: 1080232 Hom.: 6536 AF XY: 0.0891 AC XY: 48563 AN XY: 545120

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.0788

Gnomad4 ASJ exome AF: 0.0957

Gnomad4 EAS exome AF: 0.396

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.102

Gnomad4 NFE exome AF: 0.0663

Gnomad4 OTH exome AF: 0.0982

GnomAD4 genome AF: 0.110 AC: 16679 AN: 152234 Hom.: 1293 Cov.: 33 AF XY: 0.112 AC XY: 8371 AN XY: 74426

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.0633

Gnomad4 ASJ AF: 0.0939

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0703

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0793 Hom.: 1098

Bravo AF: 0.111

Asia WGS AF: 0.234 AC: 812 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 12, 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
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.038
DANN	Benign	0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs12636856; hg19: chr3-20136959;