rs9915547

Variant names:

• chr17-46135416-T-C
• rs9915547
• NM_015443.4:c.1289+35439A>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+35439A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 151,622 control chromosomes in the GnomAD database, including 5,008 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 0.24 (5008 hom., cov: 34)
• Consequence: KANSL1 NM_015443.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 19 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 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.1289+35439A>G		intron	N/A	NP_056258.1
	KANSL1	NM_001193466.2		c.1289+35439A>G		intron	N/A	NP_001180395.1
	KANSL1	NM_001379198.1		c.1289+35439A>G		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.1289+35439A>G		intron	N/A	ENSP00000387393.3
	KANSL1	ENST00000262419.10	TSL:1	c.1289+35439A>G		intron	N/A	ENSP00000262419.6
	KANSL1	ENST00000572904.6	TSL:5	c.1289+35439A>G		intron	N/A	ENSP00000461484.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36099 AN: 151506 Hom.: 5009 Cov.: 34

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0813

Gnomad FIN AF: 0.0672

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.238 AC: 36108 AN: 151622 Hom.: 5008 Cov.: 34 AF XY: 0.227 AC XY: 16795 AN XY: 74146

African (AFR) AF: 0.358 AC: 14770 AN: 41306

American (AMR) AF: 0.214 AC: 3257 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 947 AN: 3468

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5172

South Asian (SAS) AF: 0.0810 AC: 390 AN: 4814

European-Finnish (FIN) AF: 0.0672 AC: 708 AN: 10542

Middle Eastern (MID) AF: 0.267 AC: 78 AN: 292

European-Non Finnish (NFE) AF: 0.223 AC: 15151 AN: 67848

Other (OTH) AF: 0.257 AC: 540 AN: 2104

Alfa AF: 0.221 Hom.: 2897

Bravo AF: 0.256

Asia WGS AF: 0.0480 AC: 170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.60
PhyloP100		-1.3
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: rs9915547; hg19: chr17-44212782; COSMIC: COSV52274298;