rs1816

Positions:

• chr17-46199252-A-G

Variant summary

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

The NM_001379198.1(KANSL1):​c.-90+24419T>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 152,204 control chromosomes in the GnomAD database, including 2,138 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 (2138 hom., cov: 35)
• Consequence: KANSL1 NM_001379198.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.725

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=-0.88).
• 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	Protein	UniProt
KANSL1	NM_001193465.2	c.-90+24419T>C		intron_variant			NP_001180394.1
KANSL1	NM_001379198.1	c.-90+24419T>C		intron_variant			NP_001366127.1
KANSL1	NM_001405854.1	c.-90+24419T>C		intron_variant			NP_001392783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANSL1	ENST00000572904.6	c.-90+24419T>C		intron_variant		5		ENSP00000461484	P4
KANSL1	ENST00000574590.6	c.-90+24419T>C		intron_variant		2		ENSP00000461812	A1
KANSL1	ENST00000575318.6	c.-90+24419T>C		intron_variant		5		ENSP00000461299	A1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21971 AN: 152086 Hom.: 2140 Cov.: 35

Gnomad AFR AF: 0.0434

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0746

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: 21960 AN: 152204 Hom.: 2138 Cov.: 35 AF XY: 0.135 AC XY: 10050 AN XY: 74438

Gnomad4 AFR AF: 0.0433

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0746

Gnomad4 FIN AF: 0.0656

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.183

Alfa AF: 0.168 Hom.: 314

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	-0.88
CADD	Benign	3.8
DANN	Benign	0.71

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: rs1816; hg19: chr17-44276618;