rs1468241

chr17-46118787-A-G

Variant summary

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

The NM_015443.4(KANSL1):c.1290-24086T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,048 control chromosomes in the GnomAD database, including 2,126 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 0.14 (2126 hom., cov: 34)
• Consequence: KANSL1 NM_015443.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.337

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KANSL1	NM_015443.4	c.1290-24086T>C		intron_variant		ENST00000432791.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANSL1	ENST00000432791.7	c.1290-24086T>C		intron_variant		1	NM_015443.4	P4

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21689 AN: 151930 Hom.: 2128 Cov.: 34

Gnomad AFR AF: 0.0429

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0733

Gnomad FIN AF: 0.0643

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.143 AC: 21678 AN: 152048 Hom.: 2126 Cov.: 34 AF XY: 0.133 AC XY: 9924 AN XY: 74366

Gnomad4 AFR AF: 0.0428

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0734

Gnomad4 FIN AF: 0.0643

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.180

Alfa AF: 0.204 Hom.: 2357

Bravo AF: 0.148

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	6.3
Dann	Benign	0.54

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: rs1468241; hg19: chr17-44196153;