Variant rs17662853 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015443.4(KANSL1):c.662C>T(p.Thr221Ile) variant causes a missense change. The variant allele was found at a frequency of 0.151 in 1,608,748 control chromosomes in the GnomAD database, including 20,799 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1230 hom., cov: 35)

Exomes 𝑓: 0.16 ( 19569 hom. )

Consequence

KANSL1
NM_015443.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.54

Variant links:

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]

KANSL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.5272064E-4).

BP6

Variant 17-46171482-G-A is Benign according to our data. Variant chr17-46171482-G-A is described in ClinVar as [Benign]. Clinvar id is 323791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-46171482-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KANSL1	NM_015443.4 linkuse as main transcript	c.662C>T	p.Thr221Ile	missense_variant	2/15	ENST00000432791.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANSL1	ENST00000432791.7 linkuse as main transcript	c.662C>T	p.Thr221Ile	missense_variant	2/15	1	NM_015443.4	P4

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16280

AN:

151682

Hom.:

1230

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0259

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.0708

Gnomad ASJ

AF:

0.0803

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.0828

Gnomad FIN

AF:

0.218

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.0916

GnomAD3 exomes

AF:

0.117

AC:

29267

AN:

250096

Hom.:

2337

AF XY:

0.119

AC XY:

16144

AN XY:

135118

show subpopulations

Gnomad AFR exome

AF:

0.0257

Gnomad AMR exome

AF:

0.0440

Gnomad ASJ exome

AF:

0.0771

Gnomad EAS exome

AF:

0.000652

Gnomad SAS exome

AF:

0.0959

Gnomad FIN exome

AF:

0.212

Gnomad NFE exome

AF:

0.162

Gnomad OTH exome

AF:

0.117

GnomAD4 exome

AF:

0.155

AC:

226190

AN:

1456948

Hom.:

19569

Cov.:

AF XY:

0.153

AC XY:

110776

AN XY:

724644

show subpopulations

Gnomad4 AFR exome

AF:

0.0212

Gnomad4 AMR exome

AF:

0.0471

Gnomad4 ASJ exome

AF:

0.0799

Gnomad4 EAS exome

AF:

0.000554

Gnomad4 SAS exome

AF:

0.0991

Gnomad4 FIN exome

AF:

0.215

Gnomad4 NFE exome

AF:

0.174

Gnomad4 OTH exome

AF:

0.132

GnomAD4 genome

AF:

0.107

AC:

16277

AN:

151800

Hom.:

1230

Cov.:

AF XY:

0.108

AC XY:

8041

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.0258

Gnomad4 AMR

AF:

0.0707

Gnomad4 ASJ

AF:

0.0803

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.0829

Gnomad4 FIN

AF:

0.218

Gnomad4 NFE

AF:

0.157

Gnomad4 OTH

AF:

0.0906

Alfa

AF:

0.134

Hom.:

2008

Bravo

AF:

0.0940

TwinsUK

AF:

0.176

AC:

651

ALSPAC

AF:

0.172

AC:

662

ESP6500AA

AF:

0.0322

AC:

142

ESP6500EA

AF:

0.153

AC:

1314

ExAC

AF:

0.123

AC:

14919

Asia WGS

AF:

0.0380

AC:

130

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Koolen-de Vries syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.88

.;.;.;.;D;D;D;D;D

MetaRNN

Benign

0.00095

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

P;P;P;P;P;P

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.59

N;.;.;.;.;N;.;.;.

REVEL

Benign

0.094

Sift

Uncertain

0.0090

D;.;.;.;.;D;.;.;.

Sift4G

Benign

0.17

T;T;T;.;T;T;.;.;.

Vest4

0.53

MPC

0.099

ClinPred

0.020

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.26

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over