17-46030734-C-T

Position:

• chr17-46030734-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015443.4(KANSL1):​c.*742G>A 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 151,890 control chromosomes in the GnomAD database, including 2,135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2132 hom., cov: 31)
  • Exomes 𝑓: 0.18 (3 hom.)
• Consequence: KANSL1 NM_015443.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.217

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-46030734-C-T is Benign according to our data. Variant chr17-46030734-C-T is described in ClinVar as [Benign]. Clinvar id is 323751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KANSL1	NM_015443.4	c.*742G>A		3_prime_UTR_variant	15/15	ENST00000432791.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANSL1	ENST00000432791.7	c.*742G>A		3_prime_UTR_variant	15/15	1	NM_015443.4	P4

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21796 AN: 151606 Hom.: 2134 Cov.: 31

Gnomad AFR AF: 0.0432

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.0738

Gnomad FIN AF: 0.0654

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.181 AC: 30 AN: 166 Hom.: 3 Cov.: 0 AF XY: 0.170 AC XY: 18 AN XY: 106

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.203

Gnomad4 OTH exome AF: 0.0833

GnomAD4 genome AF: 0.144 AC: 21785 AN: 151724 Hom.: 2132 Cov.: 31 AF XY: 0.134 AC XY: 9966 AN XY: 74108

Gnomad4 AFR AF: 0.0431

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0739

Gnomad4 FIN AF: 0.0654

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.182

Alfa AF: 0.196 Hom.: 2127

Bravo AF: 0.148

Asia WGS AF: 0.0310 AC: 109 AN: 3478

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.3
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7350928; hg19: chr17-44108100;