Variant chr17-46066848-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KANSL1	NM_015443.4 linkuse as main transcript	c.1653-116A>G		intron_variant		ENST00000432791.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANSL1	ENST00000432791.7 linkuse as main transcript	c.1653-116A>G		intron_variant		1	NM_015443.4	P4

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

Gnomad4 AFR exome

AF:

0.00602

Gnomad4 AMR exome

AF:

0.251

Gnomad4 ASJ exome

AF:

0.0271

Gnomad4 EAS exome

AF:

0.470

Gnomad4 SAS exome

AF:

0.0596

Gnomad4 FIN exome

AF:

0.0739

Gnomad4 NFE exome

AF:

0.00887

Gnomad4 OTH exome

AF:

0.0534

GnomAD4 genome

AF:

0.0474

AC:

7223

AN:

152286

Hom.:

902

Cov.:

AF XY:

0.0544

AC XY:

4054

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00688

Gnomad4 AMR

AF:

0.179

Gnomad4 ASJ

AF:

0.0294

Gnomad4 EAS

AF:

0.421

Gnomad4 SAS

AF:

0.0719

Gnomad4 FIN

AF:

0.0782

Gnomad4 NFE

AF:

0.00957

Gnomad4 OTH

AF:

0.0460

Alfa

AF:

0.0390

Hom.:

108

Bravo

AF:

0.0597

Asia WGS

AF:

0.193

AC:

670

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.58

DANN

Benign

0.73

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

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