dbSNP rs17662889: KANSL1:p.Leu138Leu (chr17-46171730-A-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015443.4(KANSL1):c.414T>G(p.Leu138Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,538,972 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 0 hom., cov: 35)

Exomes 𝑓: 0.16 ( 3 hom. )

Consequence

KANSL1
NM_015443.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.259

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 17-46171730-A-C is Benign according to our data. Variant chr17-46171730-A-C is described in ClinVar as [Benign]. Clinvar id is 323796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-46171730-A-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.259 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANSL1	NM_015443.4 link	c.414T>G	p.Leu138Leu	synonymous_variant	Exon 2 of 15	ENST00000432791.7	NP_056258.1	Q7Z3B3-1A0A024R9Y2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANSL1	ENST00000432791.7 link	c.414T>G	p.Leu138Leu	synonymous_variant	Exon 2 of 15	1	NM_015443.4	ENSP00000387393.3		Q7Z3B3-1

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17218

AN:

150176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0346

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.142

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0519

Gnomad FIN

AF:

0.0576

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.148

GnomAD3 exomes

AF:

0.120

AC:

25993

AN:

216306

Hom.:

AF XY:

0.122

AC XY:

14259

AN XY:

116802

show subpopulations

Gnomad AFR exome

AF:

0.0323

Gnomad AMR exome

AF:

0.111

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.000657

Gnomad SAS exome

AF:

0.0561

Gnomad FIN exome

AF:

0.0614

Gnomad NFE exome

AF:

0.176

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.156

AC:

215991

AN:

1388680

Hom.:

Cov.:

AF XY:

0.153

AC XY:

105613

AN XY:

688948

show subpopulations

Gnomad4 AFR exome

AF:

0.0295

Gnomad4 AMR exome

AF:

0.115

Gnomad4 ASJ exome

AF:

0.194

Gnomad4 EAS exome

AF:

0.000839

Gnomad4 SAS exome

AF:

0.0575

Gnomad4 FIN exome

AF:

0.0657

Gnomad4 NFE exome

AF:

0.178

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.114

AC:

17204

AN:

150292

Hom.:

Cov.:

AF XY:

0.107

AC XY:

7906

AN XY:

73564

show subpopulations

Gnomad4 AFR

AF:

0.0344

Gnomad4 AMR

AF:

0.142

Gnomad4 ASJ

AF:

0.181

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0516

Gnomad4 FIN

AF:

0.0576

Gnomad4 NFE

AF:

0.174

Gnomad4 OTH

AF:

0.147

Alfa

AF:

0.163

Hom.:

274

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Apr 20, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Koolen-de Vries syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.5

DANN

Benign

0.68

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