17-46080231-A-G

Variant names:

• chr17-46080231-A-G
• rs17659881
• NM_015443.4:c.1533+2210T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015443.4(KANSL1):​c.1533+2210T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 148,632 control chromosomes in the GnomAD database, including 2,066 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (2066 hom., cov: 28)
• Consequence: KANSL1 NM_015443.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.865
• Publications: 26 publications found

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]

KANSL1 Gene-Disease associations (from GenCC):

• Koolen-de Vries syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), ClinGen
• Koolen-de Vries syndrome due to a point mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015443.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KANSL1	NM_015443.4	MANE Select	c.1533+2210T>C		intron	N/A	NP_056258.1
	KANSL1	NM_001193466.2		c.1533+2210T>C		intron	N/A	NP_001180395.1
	KANSL1	NM_001379198.1		c.1533+2210T>C		intron	N/A	NP_001366127.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KANSL1	ENST00000432791.7	TSL:1 MANE Select	c.1533+2210T>C		intron	N/A	ENSP00000387393.3
	KANSL1	ENST00000262419.10	TSL:1	c.1533+2210T>C		intron	N/A	ENSP00000262419.6
	KANSL1	ENST00000572904.6	TSL:5	c.1533+2210T>C		intron	N/A	ENSP00000461484.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21328 AN: 148524 Hom.: 2068 Cov.: 28

Gnomad AFR AF: 0.0427

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.00161

Gnomad SAS AF: 0.0727

Gnomad FIN AF: 0.0597

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.183

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.143 AC: 21317 AN: 148632 Hom.: 2066 Cov.: 28 AF XY: 0.134 AC XY: 9705 AN XY: 72400

African (AFR) AF: 0.0426 AC: 1721 AN: 40434

American (AMR) AF: 0.175 AC: 2583 AN: 14772

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 828 AN: 3446

East Asian (EAS) AF: 0.00161 AC: 8 AN: 4968

South Asian (SAS) AF: 0.0728 AC: 339 AN: 4656

European-Finnish (FIN) AF: 0.0597 AC: 588 AN: 9844

Middle Eastern (MID) AF: 0.219 AC: 61 AN: 278

European-Non Finnish (NFE) AF: 0.217 AC: 14575 AN: 67308

Other (OTH) AF: 0.180 AC: 366 AN: 2030

Alfa AF: 0.159 Hom.: 377

Bravo AF: 0.148

Asia WGS AF: 0.0310 AC: 109 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.34
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17659881; hg19: chr17-44157597;