3-20072497-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003884.5(KAT2B):c.430+38C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 1,594,146 control chromosomes in the GnomAD database, including 126,230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (13317 hom., cov: 32)
  • Exomes 𝑓: 0.39 (112913 hom.)
• Consequence: KAT2B NM_003884.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.974

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-20072497-C-A is Benign according to our data. Variant chr3-20072497-C-A is described in ClinVar as [Benign]. Clinvar id is 1259575.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KAT2B	NM_003884.5	c.430+38C>A		intron_variant		ENST00000263754.5
KAT2B	XM_005265528.5	c.430+38C>A		intron_variant
KAT2B	XM_047449147.1	c.139+38C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KAT2B	ENST00000263754.5	c.430+38C>A		intron_variant		1	NM_003884.5	P1
KAT2B	ENST00000426228.1	n.210+38C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62817 AN: 151930 Hom.: 13295 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.382

GnomAD3 exomes AF: 0.399 AC: 99675 AN: 249568 Hom.: 20506 AF XY: 0.400 AC XY: 53922 AN XY: 134910

Gnomad AFR exome AF: 0.497

Gnomad AMR exome AF: 0.378

Gnomad ASJ exome AF: 0.215

Gnomad EAS exome AF: 0.435

Gnomad SAS exome AF: 0.483

Gnomad FIN exome AF: 0.399

Gnomad NFE exome AF: 0.381

Gnomad OTH exome AF: 0.371

GnomAD4 exome AF: 0.392 AC: 565342 AN: 1442100 Hom.: 112913 Cov.: 27 AF XY: 0.394 AC XY: 282920 AN XY: 718148

Gnomad4 AFR exome AF: 0.495

Gnomad4 AMR exome AF: 0.385

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.441

Gnomad4 SAS exome AF: 0.480

Gnomad4 FIN exome AF: 0.395

Gnomad4 NFE exome AF: 0.386

Gnomad4 OTH exome AF: 0.385

GnomAD4 genome AF: 0.414 AC: 62880 AN: 152046 Hom.: 13317 Cov.: 32 AF XY: 0.415 AC XY: 30874 AN XY: 74320

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.378

Alfa AF: 0.372 Hom.: 2834

Bravo AF: 0.415

Asia WGS AF: 0.441 AC: 1536 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	9.5
Dann	Benign	0.45

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: rs3749180; hg19: chr3-20113989; COSMIC: COSV55427562;