17-46030240-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015443.4(KANSL1):c.*1235_*1236insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 150,202 control chromosomes in the GnomAD database, including 2,111 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (2110 hom., cov: 27)
  • Exomes 𝑓: 0.084 (1 hom.)
• Consequence: KANSL1 NM_015443.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.604

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 -10 ACMG points.

• BP6: Variant 17-46030240-A-AT is Benign according to our data. Variant chr17-46030240-A-AT is described in ClinVar as [Benign]. Clinvar id is 323741.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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.*1235_*1236insA		3_prime_UTR_variant	15/15	ENST00000432791.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANSL1	ENST00000432791.7	c.*1235_*1236insA		3_prime_UTR_variant	15/15	1	NM_015443.4	P4

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21632 AN: 149672 Hom.: 2112 Cov.: 27

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.00214

Gnomad SAS AF: 0.0750

Gnomad FIN AF: 0.0647

Gnomad MID AF: 0.221

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.187

GnomAD4 exome AF: 0.0841 AC: 36 AN: 428 Hom.: 1 Cov.: 0 AF XY: 0.0781 AC XY: 20 AN XY: 256

Gnomad4 FIN exome AF: 0.0853

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.144 AC: 21620 AN: 149774 Hom.: 2110 Cov.: 27 AF XY: 0.135 AC XY: 9884 AN XY: 73058

Gnomad4 AFR AF: 0.0430

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.00214

Gnomad4 SAS AF: 0.0749

Gnomad4 FIN AF: 0.0647

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.184

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MAPT-Related Spectrum Disorders Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs140510364; hg19: chr17-44107606;