rs2158258

chr17-46086443-A-Cchr17-46086443-A-Gchr17-46086443-A-T

Variant summary

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

The NM_015443.4(KANSL1):c.1432-3901T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,058 control chromosomes in the GnomAD database, including 22,683 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 0.54 (22683 hom., cov: 32)
• Consequence: KANSL1 NM_015443.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800

Genes affected

KANSL1 (HGNC:24565): (KAT8 regulatory NSL complex subunit 1) This gene encodes a nuclear protein that is a subunit of two protein complexes involved with histone acetylation, the MLL1 complex and the NSL1 complex. The encoded protein has been implicated in a variety of cellular processes including enhancer regulation, cell proliferation, and mitosis. Mutations in this gene are associated with Koolen-de Vries Syndrome. [provided by RefSeq, May 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KANSL1	NM_015443.4	c.1432-3901T>G		intron_variant		ENST00000432791.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANSL1	ENST00000432791.7	c.1432-3901T>G		intron_variant		1	NM_015443.4	P4

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82243 AN: 151940 Hom.: 22669 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.541 AC: 82298 AN: 152058 Hom.: 22683 Cov.: 32 AF XY: 0.542 AC XY: 40264 AN XY: 74344

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.887

Gnomad4 SAS AF: 0.407

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.567

Alfa AF: 0.554 Hom.: 29513

Bravo AF: 0.556

Asia WGS AF: 0.609 AC: 2117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	3.4
Dann	Benign	0.44

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: rs2158258; hg19: chr17-44163809;