17-46066848-T-C

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

2

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]

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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
KANSL1NM_015443.4 linkuse as main transcriptc.1653-116A>G intron_variant ENST00000432791.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KANSL1ENST00000432791.7 linkuse as main transcriptc.1653-116A>G intron_variant 1 NM_015443.4 P4

Frequencies

GnomAD3 genomes
AF:
0.0473
AC:
7202
AN:
152168
Hom.:
893
Cov.:
32
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.:
32
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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 18, 2018This 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.

Other links and lift over

dbSNP: rs2301732; hg19: chr17-44144214; COSMIC: COSV52267665; API