NM_003884.5:c.304-12262C>T

Variant names:

• chr3-20060071-C-T
• rs9874923
• NM_003884.5:c.304-12262C>T

Variant summary

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

The NM_003884.5(KAT2B):​c.304-12262C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,084 control chromosomes in the GnomAD database, including 12,350 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 (12350 hom., cov: 34)
• Consequence: KAT2B NM_003884.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT2B	NM_003884.5	c.304-12262C>T		intron_variant	Intron 1 of 17	ENST00000263754.5	NP_003875.3
KAT2B	XM_005265528.5	c.304-12262C>T		intron_variant	Intron 1 of 16		XP_005265585.1
KAT2B	XM_047449147.1	c.-192-11293C>T		intron_variant	Intron 1 of 19		XP_047305103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT2B	ENST00000263754.5	c.304-12262C>T		intron_variant	Intron 1 of 17	1	NM_003884.5	ENSP00000263754.4
KAT2B	ENST00000426228.1	n.84-12262C>T		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60679 AN: 151966 Hom.: 12347 Cov.: 34

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.399 AC: 60703 AN: 152084 Hom.: 12350 Cov.: 34 AF XY: 0.398 AC XY: 29552 AN XY: 74306

African (AFR) AF: 0.361 AC: 14972 AN: 41498

American (AMR) AF: 0.305 AC: 4665 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1580 AN: 3472

East Asian (EAS) AF: 0.443 AC: 2289 AN: 5164

South Asian (SAS) AF: 0.325 AC: 1569 AN: 4822

European-Finnish (FIN) AF: 0.480 AC: 5061 AN: 10548

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29167 AN: 67978

Other (OTH) AF: 0.411 AC: 867 AN: 2110

Alfa AF: 0.397 Hom.: 8642

Bravo AF: 0.386

Asia WGS AF: 0.382 AC: 1328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.60
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: rs9874923; hg19: chr3-20101563;