Genetic Variant ENST00000572218.5:n.7894_7895insAGAGGGC (chr17-46031116-A-AGCCCTCT) – 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.7894_7895insAGAGGGC 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 0.142 in 273,302 control chromosomes in the GnomAD database, including 3,792 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 2096 hom., cov: 28)

Exomes 𝑓: 0.14 ( 1696 hom. )

Consequence

KANSL1
ENST00000572218.5 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.11

Publications

3 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 = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANSL1	NM_015443.4 link	c.359_360insAGAGGGC		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.359_360insAGAGGGC		3_prime_UTR_variant	Exon 15 of 15	1	NM_015443.4	ENSP00000387393.3		Q7Z3B3-1

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21717

AN:

151880

Hom.:

2098

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0430

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.239

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0733

Gnomad FIN

AF:

0.0649

Gnomad MID

AF:

0.213

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.183

GnomAD4 exome

AF:

0.140

AC:

17029

AN:

121304

Hom.:

1696

Cov.:

AF XY:

0.138

AC XY:

8736

AN XY:

63218

show subpopulations

African (AFR)

AF:

0.0384

AC:

193

AN:

5022

American (AMR)

AF:

0.131

AC:

821

AN:

6246

Ashkenazi Jewish (ASJ)

AF:

0.208

AC:

857

AN:

4122

East Asian (EAS)

AF:

0.000219

AC:

AN:

9118

South Asian (SAS)

AF:

0.0567

AC:

645

AN:

11376

European-Finnish (FIN)

AF:

0.0584

AC:

348

AN:

5960

Middle Eastern (MID)

AF:

0.169

AC:

AN:

490

European-Non Finnish (NFE)

AF:

0.181

AC:

13033

AN:

72032

Other (OTH)

AF:

0.151

AC:

1047

AN:

6938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

659

1318

1977

2636

3295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.143

AC:

21706

AN:

151998

Hom.:

2096

Cov.:

AF XY:

0.134

AC XY:

9933

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.0429

AC:

1778

AN:

41492

American (AMR)

AF:

0.175

AC:

2663

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

828

AN:

3464

East Asian (EAS)

AF:

0.00155

AC:

AN:

5174

South Asian (SAS)

AF:

0.0733

AC:

353

AN:

4814

European-Finnish (FIN)

AF:

0.0649

AC:

688

AN:

10608

Middle Eastern (MID)

AF:

0.209

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.217

AC:

14699

AN:

67888

Other (OTH)

AF:

0.180

AC:

379

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

876

1752

2629

3505

4381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.157

Hom.:

224

Bravo

AF:

0.147

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Syndromic intellectual disability

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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ENST00000572218.5:n.7894_7895insAGAGGGC

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