Genetic Variant KANSL1:c.1653-116A>G (chr17-46066848-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015443.4(KANSL1):c.1653-116A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0527 in 712,794 control chromosomes in the GnomAD database, including 5,548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 902 hom., cov: 32)

Exomes 𝑓: 0.054 ( 4646 hom. )

Consequence

KANSL1
NM_015443.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.158

Publications

0 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, Labcorp Genetics (formerly Invitae), ClinGen, G2P
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 17-46066848-T-C is Benign according to our data. Variant chr17-46066848-T-C is described in ClinVar as Benign. ClinVar VariationId is 674896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015443.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KANSL1	NM_015443.4	MANE Select	c.1653-116A>G	intron	N/A	NP_056258.1	Q7Z3B3-1
KANSL1	NM_001193466.2		c.1653-116A>G	intron	N/A	NP_001180395.1	Q7Z3B3-1
KANSL1	NM_001379198.1		c.1653-116A>G	intron	N/A	NP_001366127.1	Q7Z3B3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KANSL1	ENST00000432791.7	TSL:1 MANE Select	c.1653-116A>G	intron	N/A	ENSP00000387393.3	Q7Z3B3-1
KANSL1	ENST00000262419.10	TSL:1	c.1653-116A>G	intron	N/A	ENSP00000262419.6	Q7Z3B3-1
KANSL1	ENST00000918919.1		c.1653-116A>G	intron	N/A	ENSP00000588978.1

Frequencies

GnomAD3 genomes

AF:

0.0473

AC:

7202

AN:

152168

Hom.:

893

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00690

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.421

Gnomad SAS

AF:

0.0721

Gnomad FIN

AF:

0.0782

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00956

Gnomad OTH

AF:

0.0441

GnomAD4 exome

AF:

0.0541

AC:

30340

AN:

560508

Hom.:

4646

AF XY:

0.0534

AC XY:

15521

AN XY:

290676

show subpopulations

African (AFR)

AF:

0.00602

AC:

AN:

14630

American (AMR)

AF:

0.251

AC:

4943

AN:

19708

Ashkenazi Jewish (ASJ)

AF:

0.0271

AC:

392

AN:

14476

East Asian (EAS)

AF:

0.470

AC:

14938

AN:

31784

South Asian (SAS)

AF:

0.0596

AC:

2783

AN:

46656

European-Finnish (FIN)

AF:

0.0739

AC:

2295

AN:

31074

Middle Eastern (MID)

AF:

0.0152

AC:

AN:

2498

European-Non Finnish (NFE)

AF:

0.00887

AC:

3281

AN:

370058

Other (OTH)

AF:

0.0534

AC:

1582

AN:

29624

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1084

2169

3253

4338

5422

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

210

420

630

840

1050

<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:

0.0474

AC:

7223

AN:

152286

Hom.:

902

Cov.:

AF XY:

0.0544

AC XY:

4054

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00688

AC:

286

AN:

41576

American (AMR)

AF:

0.179

AC:

2730

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0294

AC:

102

AN:

3472

East Asian (EAS)

AF:

0.421

AC:

2177

AN:

5170

South Asian (SAS)

AF:

0.0719

AC:

347

AN:

4824

European-Finnish (FIN)

AF:

0.0782

AC:

830

AN:

10618

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00957

AC:

651

AN:

68016

Other (OTH)

AF:

0.0460

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

271

541

812

1082

1353

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.0390

Hom.:

108

Bravo

AF:

0.0597

Asia WGS

AF:

0.193

AC:

670

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.58

(source)

DANN

Benign

0.73

PhyloP100

-0.16

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over