rs1078997

Positions:

• chr17-46032477-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015443.4(KANSL1):​c.2838-178T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 501,908 control chromosomes in the GnomAD database, including 7,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1918 hom., cov: 32)
  • Exomes 𝑓: 0.17 (6034 hom.)
• Consequence: KANSL1 NM_015443.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.257

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-46032477-A-G is Benign according to our data. Variant chr17-46032477-A-G is described in ClinVar as [Benign]. Clinvar id is 1244049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANSL1	NM_015443.4	c.2838-178T>C		intron_variant		ENST00000432791.7	NP_056258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANSL1	ENST00000432791.7	c.2838-178T>C		intron_variant		1	NM_015443.4	ENSP00000387393	P4

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22036 AN: 151974 Hom.: 1909 Cov.: 32

Gnomad AFR AF: 0.0826

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.167 AC: 58577 AN: 349816 Hom.: 6034 Cov.: 5 AF XY: 0.167 AC XY: 30094 AN XY: 179884

Gnomad4 AFR exome AF: 0.0839

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.137

Gnomad4 EAS exome AF: 0.413

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.147

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.145 AC: 22065 AN: 152092 Hom.: 1918 Cov.: 32 AF XY: 0.149 AC XY: 11043 AN XY: 74350

Gnomad4 AFR AF: 0.0828

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.170

Alfa AF: 0.150 Hom.: 3111

Bravo AF: 0.144

Asia WGS AF: 0.330 AC: 1147 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.097
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

Other links and lift over

dbSNP: rs1078997; hg19: chr17-44109843;