chr17-46030590-GA-G

Position:

• chr17-46030590-GA-G

Variant summary

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

The NM_015443.4(KANSL1):​c.*885del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0783 in 142,222 control chromosomes in the GnomAD database, including 1,173 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.078 (1173 hom., cov: 23)
  • Exomes 𝑓: 0.20 (0 hom.)
• Consequence: KANSL1 NM_015443.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• 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 -10 ACMG points.

• BP6: Variant 17-46030590-GA-G is Benign according to our data. Variant chr17-46030590-GA-G is described in ClinVar as [Benign]. Clinvar id is 323749.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KANSL1	NM_015443.4	c.*885del		3_prime_UTR_variant	15/15	ENST00000432791.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANSL1	ENST00000432791.7	c.*885del		3_prime_UTR_variant	15/15	1	NM_015443.4	P4

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11107 AN: 142150 Hom.: 1167 Cov.: 23

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0352

Gnomad ASJ AF: 0.0345

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.00787

Gnomad FIN AF: 0.0235

Gnomad MID AF: 0.0649

Gnomad NFE AF: 0.00718

Gnomad OTH AF: 0.0606

GnomAD4 exome AF: 0.200 AC: 6 AN: 30 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 3 AN XY: 18

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.0783 AC: 11128 AN: 142192 Hom.: 1173 Cov.: 23 AF XY: 0.0782 AC XY: 5380 AN XY: 68814

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.0353

Gnomad4 ASJ AF: 0.0345

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.00746

Gnomad4 FIN AF: 0.0235

Gnomad4 NFE AF: 0.00720

Gnomad4 OTH AF: 0.0601

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Syndromic intellectual disability Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs5820607; hg19: chr17-44107956;