rs17574824

Positions:

• chr17-46037741-C-T

Variant summary

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

The NM_015443.4(KANSL1):​c.2541+797G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,256 control chromosomes in the GnomAD database, including 2,131 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 0.14 (2131 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: KANSL1 NM_015443.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.87

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANSL1	NM_015443.4	c.2541+797G>A		intron_variant		ENST00000432791.7	NP_056258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANSL1	ENST00000432791.7	c.2541+797G>A		intron_variant		1	NM_015443.4	ENSP00000387393.3

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21824 AN: 152134 Hom.: 2133 Cov.: 33

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0737

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.143 AC: 21813 AN: 152252 Hom.: 2131 Cov.: 33 AF XY: 0.134 AC XY: 9989 AN XY: 74450

Gnomad4 AFR AF: 0.0429

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0738

Gnomad4 FIN AF: 0.0648

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.182

Alfa AF: 0.162 Hom.: 396

Bravo AF: 0.148

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.026
DANN	Benign	0.20

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: rs17574824; hg19: chr17-44115107;