17-46111701-A-G

Variant names:

• chr17-46111701-A-G
• rs7225002
• NM_015443.4:c.1290-17000T>C

Variant summary

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

The ENST00000432791.7(KANSL1):​c.1290-17000T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 151,488 control chromosomes in the GnomAD database, including 11,880 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 0.39 (11880 hom., cov: 34)
• Consequence: KANSL1 ENST00000432791.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398
• Publications: 49 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000432791.7. 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.1290-17000T>C		intron	N/A	NP_056258.1
	KANSL1	NM_001193466.2		c.1290-17000T>C		intron	N/A	NP_001180395.1
	KANSL1	NM_001379198.1		c.1290-17000T>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.1290-17000T>C		intron	N/A	ENSP00000387393.3
	KANSL1	ENST00000262419.10	TSL:1	c.1290-17000T>C		intron	N/A	ENSP00000262419.6
	KANSL1	ENST00000572904.6	TSL:5	c.1290-17000T>C		intron	N/A	ENSP00000461484.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59499 AN: 151370 Hom.: 11878 Cov.: 34

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.393 AC: 59527 AN: 151488 Hom.: 11880 Cov.: 34 AF XY: 0.390 AC XY: 28855 AN XY: 74080

African (AFR) AF: 0.390 AC: 16149 AN: 41390

American (AMR) AF: 0.464 AC: 7081 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1319 AN: 3448

East Asian (EAS) AF: 0.427 AC: 2208 AN: 5174

South Asian (SAS) AF: 0.235 AC: 1125 AN: 4794

European-Finnish (FIN) AF: 0.362 AC: 3820 AN: 10538

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26379 AN: 67596

Other (OTH) AF: 0.394 AC: 826 AN: 2096

Alfa AF: 0.396 Hom.: 36555

Bravo AF: 0.409

Asia WGS AF: 0.279 AC: 971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.4
DANN	Benign	0.61
PhyloP100		-0.40
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: rs7225002; hg19: chr17-44189067;