dbSNP rs17652961: KANSL1:n.8022C>T (chr17-46030989-G-A) – 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.8022C>T 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 156,712 control chromosomes in the GnomAD database, including 2,197 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 ( 2130 hom., cov: 31)

Exomes 𝑓: 0.14 ( 67 hom. )

Consequence

KANSL1
ENST00000572218.5 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.877

Publications

28 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=-0.89).

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.*487C>T		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.*487C>T		3_prime_UTR_variant	Exon 15 of 15	1	NM_015443.4	ENSP00000387393.3		Q7Z3B3-1

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21806

AN:

152030

Hom.:

2132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0430

Gnomad AMI

AF:

0.276

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0737

Gnomad FIN

AF:

0.0649

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.184

GnomAD4 exome

AF:

0.142

AC:

650

AN:

4564

Hom.:

Cov.:

AF XY:

0.145

AC XY:

337

AN XY:

2328

show subpopulations

African (AFR)

AF:

0.0429

AC:

AN:

140

American (AMR)

AF:

0.106

AC:

AN:

442

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

AN:

132

East Asian (EAS)

AF:

0.00

AC:

AN:

162

South Asian (SAS)

AF:

0.0476

AC:

AN:

168

European-Finnish (FIN)

AF:

0.0513

AC:

AN:

156

Middle Eastern (MID)

AF:

0.300

AC:

AN:

European-Non Finnish (NFE)

AF:

0.165

AC:

518

AN:

3130

Other (OTH)

AF:

0.174

AC:

AN:

224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.143

AC:

21795

AN:

152148

Hom.:

2130

Cov.:

AF XY:

0.134

AC XY:

9979

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.0429

AC:

1780

AN:

41506

American (AMR)

AF:

0.175

AC:

2680

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

833

AN:

3470

East Asian (EAS)

AF:

0.00174

AC:

AN:

5186

South Asian (SAS)

AF:

0.0737

AC:

355

AN:

4816

European-Finnish (FIN)

AF:

0.0649

AC:

688

AN:

10596

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.217

AC:

14753

AN:

67986

Other (OTH)

AF:

0.182

AC:

383

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

913

1826

2739

3652

4565

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.197

Hom.:

1436

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

-0.89

CADD

Benign

1.2

(source)

DANN

Benign

0.63

PhyloP100

-0.88

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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rs17652961

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