rs9332441

chr12-48677462-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017822.4(KANSL2):c.545+1574A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 151,934 control chromosomes in the GnomAD database, including 7,119 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 0.28 (7119 hom., cov: 31)
• Consequence: KANSL2 NM_017822.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

Genes affected

KANSL2 (HGNC:26024): (KAT8 regulatory NSL complex subunit 2) Involved in histone H4-K16 acetylation; histone H4-K5 acetylation; and histone H4-K8 acetylation. Located in several cellular components, including actin cytoskeleton; cytosol; and nucleoplasm. Part of histone acetyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KANSL2	NM_017822.4	c.545+1574A>G		intron_variant		ENST00000420613.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANSL2	ENST00000420613.7	c.545+1574A>G		intron_variant		1	NM_017822.4	P1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42102 AN: 151816 Hom.: 7106 Cov.: 31

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.277 AC: 42134 AN: 151934 Hom.: 7119 Cov.: 31 AF XY: 0.291 AC XY: 21614 AN XY: 74236

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.499

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.293

Alfa AF: 0.271 Hom.: 3267

Bravo AF: 0.279

Asia WGS AF: 0.581 AC: 2019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	1.5
Dann	Benign	0.87

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: rs9332441; hg19: chr12-49071245;