17-46030590-GAAAA-GAAAAA

Variant names:

• chr17-46030590-G-GA
• rs5820607
• NM_015443.4:c.*885dupT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_015443.4(KANSL1):​c.*885dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 142,312 control chromosomes in the GnomAD database, including 1,760 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (1760 hom., cov: 23)
  • Exomes 𝑓: 0.088 (0 hom.)
• Consequence: KANSL1 NM_015443.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANSL1	NM_015443.4	c.*885dupT		3_prime_UTR_variant	Exon 15 of 15	ENST00000432791.7	NP_056258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANSL1	ENST00000432791	c.*885dupT		3_prime_UTR_variant	Exon 15 of 15	1	NM_015443.4	ENSP00000387393.3

Frequencies

GnomAD3 genomes AF: 0.149 AC: 21138 AN: 142236 Hom.: 1760 Cov.: 23

Gnomad AFR AF: 0.0815

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.276

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.0882 AC: 3 AN: 34 Hom.: 0 Cov.: 0 AF XY: 0.0909 AC XY: 2 AN XY: 22

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0417

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.149 AC: 21138 AN: 142278 Hom.: 1760 Cov.: 23 AF XY: 0.152 AC XY: 10501 AN XY: 68876

Gnomad4 AFR AF: 0.0814

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.172

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs5820607; hg19: chr17-44107956;