chr17-46033166-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_015443.4(KANSL1):c.2751C>T(p.Phe917Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,600,854 control chromosomes in the GnomAD database, including 32,471 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2102 hom., cov: 32)

Exomes 𝑓: 0.19 ( 30369 hom. )

Consequence

KANSL1
NM_015443.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0610

Publications

32 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 17-46033166-G-A is Benign according to our data. Variant chr17-46033166-G-A is described in ClinVar as Benign. ClinVar VariationId is 323765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.061 with no splicing effect.

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.2751C>T	p.Phe917Phe	synonymous_variant	Exon 13 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.2751C>T	p.Phe917Phe	synonymous_variant	Exon 13 of 15	1	NM_015443.4	ENSP00000387393.3		Q7Z3B3-1

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21742

AN:

152008

Hom.:

2103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0428

Gnomad AMI

AF:

0.274

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0738

Gnomad FIN

AF:

0.0649

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.180

GnomAD2 exomes

AF:

0.143

AC:

33062

AN:

231482

AF XY:

0.146

show subpopulations

Gnomad AFR exome

AF:

0.0384

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.254

Gnomad EAS exome

AF:

0.000623

Gnomad FIN exome

AF:

0.0664

Gnomad NFE exome

AF:

0.211

Gnomad OTH exome

AF:

0.176

GnomAD4 exome

AF:

0.193

AC:

279548

AN:

1448726

Hom.:

30369

Cov.:

AF XY:

0.190

AC XY:

137063

AN XY:

719498

show subpopulations

African (AFR)

AF:

0.0363

AC:

1208

AN:

33298

American (AMR)

AF:

0.124

AC:

5411

AN:

43584

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

6600

AN:

25802

East Asian (EAS)

AF:

0.000889

AC:

AN:

39378

South Asian (SAS)

AF:

0.0789

AC:

6647

AN:

84254

European-Finnish (FIN)

AF:

0.0719

AC:

3785

AN:

52634

Middle Eastern (MID)

AF:

0.201

AC:

1156

AN:

5744

European-Non Finnish (NFE)

AF:

0.221

AC:

244101

AN:

1104076

Other (OTH)

AF:

0.177

AC:

10605

AN:

59956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.430

Heterozygous variant carriers

11077

22153

33230

44306

55383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8170

16340

24510

32680

40850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.143

AC:

21733

AN:

152128

Hom.:

2102

Cov.:

AF XY:

0.134

AC XY:

9950

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0427

AC:

1772

AN:

41526

American (AMR)

AF:

0.175

AC:

2679

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

834

AN:

3472

East Asian (EAS)

AF:

0.00155

AC:

AN:

5170

South Asian (SAS)

AF:

0.0739

AC:

356

AN:

4820

European-Finnish (FIN)

AF:

0.0649

AC:

689

AN:

10612

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.217

AC:

14711

AN:

67946

Other (OTH)

AF:

0.178

AC:

373

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

914

1827

2741

3654

4568

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

234

468

702

936

1170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.194

Hom.:

2727

Bravo

AF:

0.148

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Koolen-de Vries syndrome

Benign:1

Feb 04, 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

-0.46

CADD

Benign

1.1

(source)

DANN

Benign

0.87

PhyloP100

0.061

Mutation Taster

=99/1

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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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