Genetic Variant KANSL1:n.8770dupA (chr17-46030240-A-AT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000572218.5(KANSL1):n.8770dupA 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 0.144 in 150,202 control chromosomes in the GnomAD database, including 2,111 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 2110 hom., cov: 27)

Exomes 𝑓: 0.084 ( 1 hom. )

Consequence

KANSL1
ENST00000572218.5 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.604

Publications

2 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANSL1	NM_015443.4 link	c.*1235dupA		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.*1235dupA		3_prime_UTR_variant	Exon 15 of 15	1	NM_015443.4	ENSP00000387393.3		Q7Z3B3-1

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

21632

AN:

149672

Hom.:

2112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0431

Gnomad AMI

AF:

0.276

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.00214

Gnomad SAS

AF:

0.0750

Gnomad FIN

AF:

0.0647

Gnomad MID

AF:

0.221

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.187

GnomAD4 exome

AF:

0.0841

AC:

AN:

428

Hom.:

Cov.:

AF XY:

0.0781

AC XY:

AN XY:

256

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0853

AC:

AN:

422

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.144

AC:

21620

AN:

149774

Hom.:

2110

Cov.:

AF XY:

0.135

AC XY:

9884

AN XY:

73058

show subpopulations

African (AFR)

AF:

0.0430

AC:

1752

AN:

40758

American (AMR)

AF:

0.176

AC:

2650

AN:

15026

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

833

AN:

3454

East Asian (EAS)

AF:

0.00214

AC:

AN:

5130

South Asian (SAS)

AF:

0.0749

AC:

355

AN:

4738

European-Finnish (FIN)

AF:

0.0647

AC:

643

AN:

9940

Middle Eastern (MID)

AF:

0.219

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.218

AC:

14683

AN:

67468

Other (OTH)

AF:

0.184

AC:

379

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

886

1771

2657

3542

4428

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0334

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.60

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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chr17-46030240-A-AT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over