rs730086

Variant names:

• chr17-42119739-G-A
• rs730086
• NM_021078.3:c.700-21C>T

Variant summary

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

The NM_021078.3(KAT2A):​c.700-21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,573,456 control chromosomes in the GnomAD database, including 100,910 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 0.45 (19666 hom., cov: 32)
  • Exomes 𝑓: 0.33 (81244 hom.)
• Consequence: KAT2A NM_021078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 19 publications found

Genes affected

KAT2A (HGNC:4201): (lysine acetyltransferase 2A) KAT2A, or GCN5, is a histone acetyltransferase (HAT) that functions primarily as a transcriptional activator. It also functions as a repressor of NF-kappa-B (see MIM 164011) by promoting ubiquitination of the NF-kappa-B subunit RELA (MIM 164014) in a HAT-independent manner (Mao et al., 2009 [PubMed 19339690]).[supplied by OMIM, Sep 2009]

ENSG00000267261 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT2A	NM_021078.3	c.700-21C>T		intron_variant	Intron 4 of 17	ENST00000225916.10	NP_066564.2
KAT2A	NM_001376227.1	c.700-21C>T		intron_variant	Intron 4 of 17		NP_001363156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT2A	ENST00000225916.10	c.700-21C>T		intron_variant	Intron 4 of 17	1	NM_021078.3	ENSP00000225916.5
ENSG00000267261	ENST00000592574.1	c.802-21C>T		intron_variant	Intron 7 of 7	5		ENSP00000468367.1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68722 AN: 151800 Hom.: 19618 Cov.: 32

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.414

GnomAD2 exomes AF: 0.330 AC: 72007 AN: 217900 AF XY: 0.325

Gnomad AFR exome AF: 0.828

Gnomad AMR exome AF: 0.214

Gnomad ASJ exome AF: 0.353

Gnomad EAS exome AF: 0.161

Gnomad FIN exome AF: 0.339

Gnomad NFE exome AF: 0.327

Gnomad OTH exome AF: 0.315

GnomAD4 exome AF: 0.326 AC: 463650 AN: 1421538 Hom.: 81244 Cov.: 31 AF XY: 0.324 AC XY: 227940 AN XY: 703644

African (AFR) AF: 0.839 AC: 26967 AN: 32160

American (AMR) AF: 0.221 AC: 8817 AN: 39842

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 8218 AN: 23584

East Asian (EAS) AF: 0.178 AC: 7017 AN: 39336

South Asian (SAS) AF: 0.281 AC: 22641 AN: 80514

European-Finnish (FIN) AF: 0.339 AC: 17686 AN: 52130

Middle Eastern (MID) AF: 0.351 AC: 1865 AN: 5306

European-Non Finnish (NFE) AF: 0.321 AC: 350184 AN: 1089996

Other (OTH) AF: 0.345 AC: 20255 AN: 58670

GnomAD4 genome AF: 0.453 AC: 68827 AN: 151918 Hom.: 19666 Cov.: 32 AF XY: 0.447 AC XY: 33158 AN XY: 74244

African (AFR) AF: 0.817 AC: 33854 AN: 41448

American (AMR) AF: 0.292 AC: 4460 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1227 AN: 3472

East Asian (EAS) AF: 0.164 AC: 845 AN: 5156

South Asian (SAS) AF: 0.290 AC: 1395 AN: 4816

European-Finnish (FIN) AF: 0.348 AC: 3676 AN: 10562

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 21987 AN: 67896

Other (OTH) AF: 0.416 AC: 876 AN: 2108

Alfa AF: 0.361 Hom.: 6237

Bravo AF: 0.465

Asia WGS AF: 0.328 AC: 1141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.035
DANN	Benign	0.59
PhyloP100		-1.3
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: rs730086; hg19: chr17-40271757;