rs1124376

Positions:

• chr3-20067054-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003884.5(KAT2B):​c.304-5279C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,106 control chromosomes in the GnomAD database, including 2,047 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 0.15 (2047 hom., cov: 32)
• Consequence: KAT2B NM_003884.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAT2B	NM_003884.5	c.304-5279C>T		intron_variant		ENST00000263754.5	NP_003875.3
KAT2B	XM_005265528.5	c.304-5279C>T		intron_variant			XP_005265585.1
KAT2B	XM_047449147.1	c.-192-4310C>T		intron_variant			XP_047305103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAT2B	ENST00000263754.5	c.304-5279C>T		intron_variant		1	NM_003884.5	ENSP00000263754	P1
KAT2B	ENST00000426228.1	n.84-5279C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22354 AN: 151988 Hom.: 2045 Cov.: 32

Gnomad AFR AF: 0.0491

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.00925

Gnomad SAS AF: 0.0967

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.147 AC: 22356 AN: 152106 Hom.: 2047 Cov.: 32 AF XY: 0.145 AC XY: 10783 AN XY: 74380

Gnomad4 AFR AF: 0.0490

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.00927

Gnomad4 SAS AF: 0.0974

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.165

Alfa AF: 0.197 Hom.: 3859

Bravo AF: 0.137

Asia WGS AF: 0.0660 AC: 228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.42

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: rs1124376; hg19: chr3-20108546;