rs9915547

Positions:

• chr17-46135416-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANSL1	NM_015443.4	c.1289+35439A>G		intron_variant		ENST00000432791.7	NP_056258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANSL1	ENST00000432791.7	c.1289+35439A>G		intron_variant		1	NM_015443.4	ENSP00000387393	P4

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

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0810

Gnomad4 FIN AF: 0.0672

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.257

Alfa AF: 0.225 Hom.: 992

Bravo AF: 0.256

Asia WGS AF: 0.0480 AC: 170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.60

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: rs9915547; hg19: chr17-44212782; COSMIC: COSV52274298;