Variant chr17-46034247-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015443.4(KANSL1):c.2580T>C(p.Phe860=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,613,590 control chromosomes in the GnomAD database, including 32,776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2136 hom., cov: 32)

Exomes 𝑓: 0.19 ( 30640 hom. )

Consequence

KANSL1
NM_015443.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.635

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 17-46034247-A-G is Benign according to our data. Variant chr17-46034247-A-G is described in ClinVar as [Benign]. Clinvar id is 323767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-46034247-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.635 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/exons	MANE	Protein	UniProt
KANSL1	NM_015443.4 linkuse as main transcript	c.2580T>C	p.Phe860=	synonymous_variant	11/15	ENST00000432791.7	NP_056258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANSL1	ENST00000432791.7 linkuse as main transcript	c.2580T>C	p.Phe860=	synonymous_variant	11/15	1	NM_015443.4	ENSP00000387393	P4

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21812

AN:

152136

Hom.:

2138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0429

Gnomad AMI

AF:

0.278

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0736

Gnomad FIN

AF:

0.0649

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.184

GnomAD3 exomes

AF:

0.145

AC:

36448

AN:

251234

Hom.:

3539

AF XY:

0.149

AC XY:

20176

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.0398

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.254

Gnomad EAS exome

AF:

0.000652

Gnomad SAS exome

AF:

0.0759

Gnomad FIN exome

AF:

0.0681

Gnomad NFE exome

AF:

0.213

Gnomad OTH exome

AF:

0.175

GnomAD4 exome

AF:

0.193

AC:

282555

AN:

1461336

Hom.:

30640

Cov.:

AF XY:

0.191

AC XY:

138803

AN XY:

726990

show subpopulations

Gnomad4 AFR exome

AF:

0.0365

Gnomad4 AMR exome

AF:

0.125

Gnomad4 ASJ exome

AF:

0.256

Gnomad4 EAS exome

AF:

0.000882

Gnomad4 SAS exome

AF:

0.0795

Gnomad4 FIN exome

AF:

0.0724

Gnomad4 NFE exome

AF:

0.222

Gnomad4 OTH exome

AF:

0.177

GnomAD4 genome

AF:

0.143

AC:

21801

AN:

152254

Hom.:

2136

Cov.:

AF XY:

0.134

AC XY:

9973

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0428

Gnomad4 AMR

AF:

0.175

Gnomad4 ASJ

AF:

0.240

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.0736

Gnomad4 FIN

AF:

0.0649

Gnomad4 NFE

AF:

0.217

Gnomad4 OTH

AF:

0.181

Alfa

AF:

0.203

Hom.:

3397

Bravo

AF:

0.148

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Koolen-de Vries syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.6

DANN

Benign

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over