17-46029951-CCTT-C

Position:

• chr17-46029951-CCTT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_015443.4(KANSL1):​c.*1522_*1524delAAG variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00174 in 148,210 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KANSL1 NM_015443.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.79

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 -10 ACMG points.

• BP6: Variant 17-46029951-CCTT-C is Benign according to our data. Variant chr17-46029951-CCTT-C is described in ClinVar as [Benign]. Clinvar id is 2647854.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00174 (258/148210) while in subpopulation AMR AF= 0.00566 (83/14666). AF 95% confidence interval is 0.00468. There are 1 homozygotes in gnomad4. There are 134 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 258 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANSL1	NM_015443.4	c.*1522_*1524delAAG		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.*1522_*1524delAAG		3_prime_UTR_variant	15/15	1	NM_015443.4	ENSP00000387393.3

Frequencies

GnomAD3 genomes AF: 0.00174 AC: 258 AN: 148088 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00567

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00136

Gnomad SAS AF: 0.00105

Gnomad FIN AF: 0.0000983

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00123

Gnomad OTH AF: 0.00200

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 318 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 194

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00174 AC: 258 AN: 148210 Hom.: 1 Cov.: 31 AF XY: 0.00185 AC XY: 134 AN XY: 72460

Gnomad4 AFR AF: 0.00187

Gnomad4 AMR AF: 0.00566

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.00105

Gnomad4 FIN AF: 0.0000983

Gnomad4 NFE AF: 0.00123

Gnomad4 OTH AF: 0.00198

Alfa AF: 0.00135 Hom.: 0

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

KANSL1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

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: rs769319125; hg19: chr17-44107317;