rs730086

Positions:

• chr17-42119739-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
KAT2A	NM_021078.3	c.700-21C>T		intron_variant		ENST00000225916.10	NP_066564.2
KAT2A	NM_001376227.1	c.700-21C>T		intron_variant			NP_001363156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAT2A	ENST00000225916.10	c.700-21C>T		intron_variant		1	NM_021078.3	ENSP00000225916.5
ENSG00000267261	ENST00000592574.1	c.802-21C>T		intron_variant		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

GnomAD3 exomes AF: 0.330 AC: 72007 AN: 217900 Hom.: 14116 AF XY: 0.325 AC XY: 38266 AN XY: 117628

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 SAS exome AF: 0.294

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

Gnomad4 AFR exome AF: 0.839

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.348

Gnomad4 EAS exome AF: 0.178

Gnomad4 SAS exome AF: 0.281

Gnomad4 FIN exome AF: 0.339

Gnomad4 NFE exome AF: 0.321

Gnomad4 OTH exome AF: 0.345

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

Gnomad4 AFR AF: 0.817

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.416

Alfa AF: 0.371 Hom.: 3613

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

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: rs730086; hg19: chr17-40271757;