rs17574361

Positions:

• chr17-46030836-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.*640T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,604 control chromosomes in the GnomAD database, including 2,129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2123 hom., cov: 31)
  • Exomes 𝑓: 0.14 (6 hom.)
• Consequence: KANSL1 NM_015443.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.69

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=-0.82).
• BP6: Variant 17-46030836-A-G is Benign according to our data. Variant chr17-46030836-A-G is described in ClinVar as [Benign]. Clinvar id is 323752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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	c.*640T>C		3_prime_UTR_variant	15/15	ENST00000432791.7	NP_056258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANSL1	ENST00000432791.7	c.*640T>C		3_prime_UTR_variant	15/15	1	NM_015443.4	ENSP00000387393	P4

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21778 AN: 152006 Hom.: 2125 Cov.: 31

Gnomad AFR AF: 0.0429

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0740

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.142 AC: 68 AN: 480 Hom.: 6 Cov.: 0 AF XY: 0.160 AC XY: 49 AN XY: 306

Gnomad4 AMR exome AF: 0.0769

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.0833

GnomAD4 genome AF: 0.143 AC: 21767 AN: 152124 Hom.: 2123 Cov.: 31 AF XY: 0.134 AC XY: 9965 AN XY: 74374

Gnomad4 AFR AF: 0.0428

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0740

Gnomad4 FIN AF: 0.0648

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.180

Alfa AF: 0.206 Hom.: 2929

Bravo AF: 0.148

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

MAPT-Related Spectrum Disorders Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.3
DANN	Benign	0.76

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: rs17574361; hg19: chr17-44108202;