17-46031438-CAATA-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_015443.4(KANSL1):c.*34_*37del variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00296 in 1,526,256 control chromosomes in the GnomAD database, including 53 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (50 hom.)
• Consequence: KANSL1 NM_015443.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.64

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 -16 ACMG points.

• BP6: Variant 17-46031438-CAATA-C is Benign according to our data. Variant chr17-46031438-CAATA-C is described in ClinVar as [Likely_benign]. Clinvar id is 323760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00292 (445/152272) while in subpopulation EAS AF= 0.0178 (92/5182). AF 95% confidence interval is 0.0148. There are 3 homozygotes in gnomad4. There are 263 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 445 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KANSL1	NM_015443.4	c.*34_*37del		3_prime_UTR_variant	15/15	ENST00000432791.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANSL1	ENST00000432791.7	c.*34_*37del		3_prime_UTR_variant	15/15	1	NM_015443.4	P4

Frequencies

GnomAD3 genomes AF: 0.00292 AC: 445 AN: 152154 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00894

Gnomad EAS AF: 0.0177

Gnomad SAS AF: 0.00579

Gnomad FIN AF: 0.0162

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00160

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00469 AC: 851 AN: 181600 Hom.: 10 AF XY: 0.00480 AC XY: 466 AN XY: 96996

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000386

Gnomad ASJ exome AF: 0.00656

Gnomad EAS exome AF: 0.0166

Gnomad SAS exome AF: 0.00529

Gnomad FIN exome AF: 0.0180

Gnomad NFE exome AF: 0.00148

Gnomad OTH exome AF: 0.00343

GnomAD4 exome AF: 0.00296 AC: 4067 AN: 1373984 Hom.: 50 AF XY: 0.00304 AC XY: 2047 AN XY: 673908

Gnomad4 AFR exome AF: 0.000125

Gnomad4 AMR exome AF: 0.000111

Gnomad4 ASJ exome AF: 0.00573

Gnomad4 EAS exome AF: 0.0349

Gnomad4 SAS exome AF: 0.00568

Gnomad4 FIN exome AF: 0.0150

Gnomad4 NFE exome AF: 0.00119

Gnomad4 OTH exome AF: 0.00261

GnomAD4 genome AF: 0.00292 AC: 445 AN: 152272 Hom.: 3 Cov.: 32 AF XY: 0.00353 AC XY: 263 AN XY: 74454

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00894

Gnomad4 EAS AF: 0.0178

Gnomad4 SAS AF: 0.00580

Gnomad4 FIN AF: 0.0162

Gnomad4 NFE AF: 0.00160

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00251 Hom.: 0

Bravo AF: 0.00151

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Syndromic intellectual disability Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

MAPT-Related Spectrum Disorders Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 17, 2018

- -

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: rs373668834; hg19: chr17-44108804;