rs2532274

Variant names:

• chr17-46169798-A-G
• rs2532274
• NM_015443.4:c.1289+1057T>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.1289+1057T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,114 control chromosomes in the GnomAD database, including 3,448 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 0.20 (3448 hom., cov: 36)
• Consequence: KANSL1 NM_015443.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.390
• Publications: 36 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANSL1	NM_015443.4	c.1289+1057T>C		intron_variant	Intron 2 of 14	ENST00000432791.7	NP_056258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANSL1	ENST00000432791.7	c.1289+1057T>C		intron_variant	Intron 2 of 14	1	NM_015443.4	ENSP00000387393.3

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30791 AN: 151998 Hom.: 3454 Cov.: 36

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0819

Gnomad FIN AF: 0.0674

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.202 AC: 30787 AN: 152114 Hom.: 3448 Cov.: 36 AF XY: 0.192 AC XY: 14270 AN XY: 74396

African (AFR) AF: 0.233 AC: 9659 AN: 41460

American (AMR) AF: 0.205 AC: 3127 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 888 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5184

South Asian (SAS) AF: 0.0820 AC: 396 AN: 4832

European-Finnish (FIN) AF: 0.0674 AC: 714 AN: 10600

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.223 AC: 15141 AN: 67982

Other (OTH) AF: 0.238 AC: 503 AN: 2110

Alfa AF: 0.216 Hom.: 6365

Bravo AF: 0.215

Asia WGS AF: 0.0420 AC: 148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.40
PhyloP100		-0.39
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: rs2532274; hg19: chr17-44247164;