rs9303525

Positions:

• chr17-46109891-A-G
• chr17-46109891-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000432791.7(KANSL1):​c.1290-15190T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 151,916 control chromosomes in the GnomAD database, including 4,474 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 0.23 (4474 hom., cov: 34)
• Consequence: KANSL1 ENST00000432791.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANSL1	NM_015443.4	c.1290-15190T>C		intron_variant		ENST00000432791.7	NP_056258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANSL1	ENST00000432791.7	c.1290-15190T>C		intron_variant		1	NM_015443.4	ENSP00000387393	P4

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34414 AN: 151798 Hom.: 4480 Cov.: 34

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0804

Gnomad FIN AF: 0.0660

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.227 AC: 34420 AN: 151916 Hom.: 4474 Cov.: 34 AF XY: 0.215 AC XY: 15980 AN XY: 74264

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0803

Gnomad4 FIN AF: 0.0660

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.249

Alfa AF: 0.218 Hom.: 1667

Bravo AF: 0.243

Asia WGS AF: 0.0460 AC: 164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.2
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs9303525; hg19: chr17-44187257;