rs2696588

Variant names:

• chr17-46145058-G-C
• rs2696588
• NM_015443.4:c.1289+25797C>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.1289+25797C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,398 control chromosomes in the GnomAD database, including 22,053 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 (22053 hom., cov: 37)
• Consequence: KANSL1 NM_015443.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209
• Publications: 7 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 (EAS) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANSL1	NM_015443.4	c.1289+25797C>G		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+25797C>G		intron_variant	Intron 2 of 14	1	NM_015443.4	ENSP00000387393.3

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81284 AN: 151280 Hom.: 22038 Cov.: 37

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.882

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.537 AC: 81340 AN: 151398 Hom.: 22053 Cov.: 37 AF XY: 0.537 AC XY: 39735 AN XY: 73986

African (AFR) AF: 0.480 AC: 19861 AN: 41378

American (AMR) AF: 0.652 AC: 9934 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1753 AN: 3450

East Asian (EAS) AF: 0.882 AC: 4568 AN: 5178

South Asian (SAS) AF: 0.381 AC: 1807 AN: 4738

European-Finnish (FIN) AF: 0.499 AC: 5238 AN: 10506

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.534 AC: 36122 AN: 67638

Other (OTH) AF: 0.566 AC: 1181 AN: 2086

Alfa AF: 0.519 Hom.: 2520

Bravo AF: 0.552

Asia WGS AF: 0.599 AC: 2081 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	4.4
DANN	Benign	0.50
PhyloP100		0.21
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: rs2696588; hg19: chr17-44222424;