17-46172742-T-C

Variant names:

• chr17-46172742-T-C
• rs2532269
• NM_015443.4:c.-89-510A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015443.4(KANSL1):​c.-89-510A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,206 control chromosomes in the GnomAD database, including 2,376 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 0.16 (2376 hom., cov: 35)
• Consequence: KANSL1 NM_015443.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANSL1	NM_015443.4	c.-89-510A>G		intron_variant	Intron 1 of 14	ENST00000432791.7	NP_056258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANSL1	ENST00000432791.7	c.-89-510A>G		intron_variant	Intron 1 of 14	1	NM_015443.4	ENSP00000387393.3

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24822 AN: 152088 Hom.: 2378 Cov.: 35

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0752

Gnomad FIN AF: 0.0655

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.163 AC: 24814 AN: 152206 Hom.: 2376 Cov.: 35 AF XY: 0.153 AC XY: 11384 AN XY: 74432

African (AFR) AF: 0.108 AC: 4470 AN: 41520

American (AMR) AF: 0.185 AC: 2835 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 843 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5188

South Asian (SAS) AF: 0.0750 AC: 362 AN: 4824

European-Finnish (FIN) AF: 0.0655 AC: 696 AN: 10618

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14848 AN: 67984

Other (OTH) AF: 0.195 AC: 412 AN: 2114

Alfa AF: 0.185 Hom.: 2954

Bravo AF: 0.171

Asia WGS AF: 0.0360 AC: 129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.75
PhyloP100		-2.0
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: rs2532269; hg19: chr17-44250108;