Genetic Variant KANSL1:n.8175T>C (chr17-46030836-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000572218.5(KANSL1):n.8175T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,604 control chromosomes in the GnomAD database, including 2,129 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 2123 hom., cov: 31)

Exomes 𝑓: 0.14 ( 6 hom. )

Consequence

KANSL1
ENST00000572218.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.69

Publications

40 publications found

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 Gene-Disease associations (from GenCC):

Koolen-de Vries syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen
Koolen-de Vries syndrome due to a point mutation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KANSL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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 rank	MANE	Protein	UniProt
KANSL1	NM_015443.4 link	c.*640T>C		3_prime_UTR_variant	Exon 15 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.*640T>C		3_prime_UTR_variant	Exon 15 of 15	1	NM_015443.4	ENSP00000387393.3		Q7Z3B3-1

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21778

AN:

152006

Hom.:

2125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0429

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0740

Gnomad FIN

AF:

0.0648

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.183

GnomAD4 exome

AF:

0.142

AC:

AN:

480

Hom.:

Cov.:

AF XY:

0.160

AC XY:

AN XY:

306

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.0769

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.190

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.155

AC:

AN:

354

Other (OTH)

AF:

0.0833

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.143

AC:

21767

AN:

152124

Hom.:

2123

Cov.:

AF XY:

0.134

AC XY:

9965

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0428

AC:

1779

AN:

41528

American (AMR)

AF:

0.175

AC:

2679

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

830

AN:

3464

East Asian (EAS)

AF:

0.00155

AC:

AN:

5172

South Asian (SAS)

AF:

0.0740

AC:

357

AN:

4822

European-Finnish (FIN)

AF:

0.0648

AC:

687

AN:

10596

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.217

AC:

14735

AN:

67962

Other (OTH)

AF:

0.180

AC:

379

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

897

1795

2692

3590

4487

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.199

Hom.:

4372

Bravo

AF:

0.148

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

MAPT-Related Spectrum Disorders

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.3

(source)

DANN

Benign

0.76

PhyloP100

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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17-46030836-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over