3-20125445-C-G

Variant names:

• chr3-20125445-C-G
• rs4858767
• NM_003884.5:c.1414-460C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003884.5(KAT2B):​c.1414-460C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,124 control chromosomes in the GnomAD database, including 14,377 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 0.41 (14377 hom., cov: 33)
• Consequence: KAT2B NM_003884.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 4 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003884.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAT2B	NM_003884.5	MANE Select	c.1414-460C>G		intron	N/A	NP_003875.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAT2B	ENST00000263754.5	TSL:1 MANE Select	c.1414-460C>G		intron	N/A	ENSP00000263754.4	Q92831
	KAT2B	ENST00000956100.1		c.1393-460C>G		intron	N/A	ENSP00000626159.1
	KAT2B	ENST00000956099.1		c.1321-460C>G		intron	N/A	ENSP00000626158.1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62880 AN: 152006 Hom.: 14347 Cov.: 33

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.414 AC: 62949 AN: 152124 Hom.: 14377 Cov.: 33 AF XY: 0.419 AC XY: 31185 AN XY: 74380

African (AFR) AF: 0.582 AC: 24161 AN: 41492

American (AMR) AF: 0.447 AC: 6837 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 520 AN: 3472

East Asian (EAS) AF: 0.531 AC: 2749 AN: 5180

South Asian (SAS) AF: 0.488 AC: 2353 AN: 4824

European-Finnish (FIN) AF: 0.380 AC: 4008 AN: 10560

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21239 AN: 67994

Other (OTH) AF: 0.372 AC: 787 AN: 2114

Alfa AF: 0.203 Hom.: 418

Bravo AF: 0.423

Asia WGS AF: 0.499 AC: 1731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.33
DANN	Benign	0.67
PhyloP100		-1.9
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: rs4858767; hg19: chr3-20166937;