chr17-46118787-A-G

Variant names:

• chr17-46118787-A-G
• rs1468241
• NM_015443.4:c.1290-24086T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 publications found

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]

KANSL1 Gene-Disease associations (from GenCC):

• Koolen-de Vries syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen
• Koolen-de Vries syndrome due to a point mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015443.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KANSL1	NM_015443.4	MANE Select	c.1290-24086T>C		intron	N/A	NP_056258.1
	KANSL1	NM_001193466.2		c.1290-24086T>C		intron	N/A	NP_001180395.1
	KANSL1	NM_001379198.1		c.1290-24086T>C		intron	N/A	NP_001366127.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KANSL1	ENST00000432791.7	TSL:1 MANE Select	c.1290-24086T>C		intron	N/A	ENSP00000387393.3
	KANSL1	ENST00000262419.10	TSL:1	c.1290-24086T>C		intron	N/A	ENSP00000262419.6
	KANSL1	ENST00000572904.6	TSL:5	c.1290-24086T>C		intron	N/A	ENSP00000461484.1

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

African (AFR) AF: 0.0428 AC: 1777 AN: 41562

American (AMR) AF: 0.175 AC: 2675 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 828 AN: 3460

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5186

South Asian (SAS) AF: 0.0734 AC: 354 AN: 4826

European-Finnish (FIN) AF: 0.0643 AC: 682 AN: 10604

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.216 AC: 14658 AN: 67822

Other (OTH) AF: 0.180 AC: 380 AN: 2106

Alfa AF: 0.185 Hom.: 3344

Bravo AF: 0.148

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.3
DANN	Benign	0.54
PhyloP100		0.34
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: rs1468241; hg19: chr17-44196153;