NM_003884.5:c.1157A>G

Variant names:

• chr3-20119604-A-G
• rs17006625
• NM_003884.5:c.1157A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003884.5(KAT2B):​c.1157A>G​(p.Asn386Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,613,994 control chromosomes in the GnomAD database, including 1,243 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (237 hom., cov: 32)
  • Exomes 𝑓: 0.013 (1006 hom.)
• Consequence: KAT2B NM_003884.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.302
• Publications: 21 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015796125).
• BP6: Variant 3-20119604-A-G is Benign according to our data. Variant chr3-20119604-A-G is described in ClinVar as Benign. ClinVar VariationId is 1229746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 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.1157A>G	p.Asn386Ser	missense	Exon 8 of 18	NP_003875.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAT2B	ENST00000263754.5	TSL:1 MANE Select	c.1157A>G	p.Asn386Ser	missense	Exon 8 of 18	ENSP00000263754.4
	KAT2B	ENST00000956100.1		c.1136A>G	p.Asn379Ser	missense	Exon 8 of 18	ENSP00000626159.1
	KAT2B	ENST00000956099.1		c.1064A>G	p.Asn355Ser	missense	Exon 7 of 17	ENSP00000626158.1

Frequencies

GnomAD3 genomes AF: 0.0337 AC: 5125 AN: 152168 Hom.: 235 Cov.: 32

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0189

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.0174

Gnomad FIN AF: 0.0337

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00334

Gnomad OTH AF: 0.0325

GnomAD2 exomes AF: 0.0328 AC: 8171 AN: 249006 AF XY: 0.0291

Gnomad AFR exome AF: 0.0722

Gnomad AMR exome AF: 0.0360

Gnomad ASJ exome AF: 0.00228

Gnomad EAS exome AF: 0.222

Gnomad FIN exome AF: 0.0340

Gnomad NFE exome AF: 0.00319

Gnomad OTH exome AF: 0.0219

GnomAD4 exome AF: 0.0125 AC: 18316 AN: 1461710 Hom.: 1006 Cov.: 31 AF XY: 0.0122 AC XY: 8842 AN XY: 727168

African (AFR) AF: 0.0741 AC: 2478 AN: 33458

American (AMR) AF: 0.0341 AC: 1523 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00256 AC: 67 AN: 26136

East Asian (EAS) AF: 0.192 AC: 7636 AN: 39690

South Asian (SAS) AF: 0.0134 AC: 1154 AN: 86256

European-Finnish (FIN) AF: 0.0314 AC: 1678 AN: 53408

Middle Eastern (MID) AF: 0.0151 AC: 87 AN: 5764

European-Non Finnish (NFE) AF: 0.00213 AC: 2368 AN: 1111906

Other (OTH) AF: 0.0219 AC: 1325 AN: 60384

GnomAD4 genome AF: 0.0337 AC: 5136 AN: 152284 Hom.: 237 Cov.: 32 AF XY: 0.0354 AC XY: 2633 AN XY: 74464

African (AFR) AF: 0.0718 AC: 2985 AN: 41566

American (AMR) AF: 0.0188 AC: 288 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.214 AC: 1105 AN: 5162

South Asian (SAS) AF: 0.0172 AC: 83 AN: 4828

European-Finnish (FIN) AF: 0.0337 AC: 358 AN: 10618

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00334 AC: 227 AN: 68030

Other (OTH) AF: 0.0322 AC: 68 AN: 2114

Alfa AF: 0.0156 Hom.: 441

Bravo AF: 0.0365

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.0649 AC: 286

ESP6500EA AF: 0.00291 AC: 25

ExAC AF: 0.0320 AC: 3883

Asia WGS AF: 0.0970 AC: 336 AN: 3478

EpiCase AF: 0.00311

EpiControl AF: 0.00320

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.025
DANN	Benign	0.21
DEOGEN2	Benign	0.23	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0046	N
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.60	N
PhyloP100		-0.30
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.17
Sift	Benign	0.92	T
Sift4G	Benign	0.85	T
Polyphen		0.0020	B
Vest4		0.020
MPC		0.35
ClinPred		0.0022	T
GERP RS		-12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.018
gMVP		0.12
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs17006625; hg19: chr3-20161096; COSMIC: COSV55427107;