chr17-46030280-A-C

Position:

• chr17-46030280-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_015443.4(KANSL1):​c.*1196T>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0048 in 152,054 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KANSL1 NM_015443.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 3.81

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 17-46030280-A-C is Benign according to our data. Variant chr17-46030280-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 323743.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0048 (730/152054) while in subpopulation NFE AF= 0.00731 (497/67982). AF 95% confidence interval is 0.00678. There are 2 homozygotes in gnomad4. There are 353 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 730 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANSL1	NM_015443.4	c.*1196T>G		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	c.*1196T>G		3_prime_UTR_variant	15/15	1	NM_015443.4	ENSP00000387393.3

Frequencies

GnomAD3 genomes AF: 0.00480 AC: 730 AN: 151938 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.00537

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00266

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00731

Gnomad OTH AF: 0.00336

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 316 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 188

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.00480 AC: 730 AN: 152054 Hom.: 2 Cov.: 31 AF XY: 0.00475 AC XY: 353 AN XY: 74350

Gnomad4 AFR AF: 0.00128

Gnomad4 AMR AF: 0.00537

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000417

Gnomad4 FIN AF: 0.00266

Gnomad4 NFE AF: 0.00731

Gnomad4 OTH AF: 0.00333

Alfa AF: 0.00526 Hom.: 0

Bravo AF: 0.00489

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Syndromic intellectual disability Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

MAPT-Related Spectrum Disorders Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Benign	0.88

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: rs137970866; hg19: chr17-44107646;