rs2696600

chr17-46138860-A-G

Variant summary

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

The NM_015443.4(KANSL1):c.1289+31995T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,222 control chromosomes in the GnomAD database, including 2,135 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 (2135 hom., cov: 35)
• Consequence: KANSL1 NM_015443.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KANSL1	NM_015443.4	c.1289+31995T>C		intron_variant		ENST00000432791.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANSL1	ENST00000432791.7	c.1289+31995T>C		intron_variant		1	NM_015443.4	P4

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21974 AN: 152104 Hom.: 2137 Cov.: 35

Gnomad AFR AF: 0.0434

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0751

Gnomad FIN AF: 0.0656

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.144 AC: 21963 AN: 152222 Hom.: 2135 Cov.: 35 AF XY: 0.135 AC XY: 10048 AN XY: 74432

Gnomad4 AFR AF: 0.0433

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0752

Gnomad4 FIN AF: 0.0656

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.184

Alfa AF: 0.197 Hom.: 1226

Bravo AF: 0.149

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	-0.84
Cadd	Benign	5.8
Dann	Benign	0.68

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: rs2696600; hg19: chr17-44216226;