3-20072128-G-A

Position:

• chr3-20072128-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003884.5(KAT2B):​c.304-205G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 152,290 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.019 (55 hom., cov: 32)
• Consequence: KAT2B NM_003884.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.92

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 3-20072128-G-A is Benign according to our data. Variant chr3-20072128-G-A is described in ClinVar as [Benign]. Clinvar id is 1287829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0192 (2928/152290) while in subpopulation NFE AF= 0.0277 (1887/68020). AF 95% confidence interval is 0.0267. There are 55 homozygotes in gnomad4. There are 1482 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2928 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAT2B	NM_003884.5	c.304-205G>A		intron_variant		ENST00000263754.5	NP_003875.3
KAT2B	XM_005265528.5	c.304-205G>A		intron_variant			XP_005265585.1
KAT2B	XM_047449147.1	c.13-205G>A		intron_variant			XP_047305103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAT2B	ENST00000263754.5	c.304-205G>A		intron_variant		1	NM_003884.5	ENSP00000263754.4
KAT2B	ENST00000426228.1	n.84-205G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 2928 AN: 152172 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.00475

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00780

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.0584

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0277

Gnomad OTH AF: 0.0138

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

GnomAD4 genome AF: 0.0192 AC: 2928 AN: 152290 Hom.: 55 Cov.: 32 AF XY: 0.0199 AC XY: 1482 AN XY: 74464

Gnomad4 AFR AF: 0.00474

Gnomad4 AMR AF: 0.00778

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00435

Gnomad4 FIN AF: 0.0584

Gnomad4 NFE AF: 0.0277

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0232 Hom.: 8

Bravo AF: 0.0149

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.72

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: rs115176719; hg19: chr3-20113620;