rs2668692

Variant names:

• chr17-46215654-G-A
• rs2668692
• NM_001379198.1:c.-90+8017C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-46215654-G-A
• chr17-46215654-G-T

Variant summary

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

The NM_001379198.1(KANSL1):​c.-90+8017C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,188 control chromosomes in the GnomAD database, including 2,137 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 (2137 hom., cov: 35)
• Consequence: KANSL1 NM_001379198.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277
• Publications: 34 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=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANSL1	NM_001379198.1	c.-90+8017C>T		intron_variant	Intron 2 of 15		NP_001366127.1
KANSL1	NM_001405854.1	c.-90+8017C>T		intron_variant	Intron 2 of 15		NP_001392783.1
KANSL1	NM_001193465.2	c.-90+8017C>T		intron_variant	Intron 2 of 15		NP_001180394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANSL1	ENST00000572904.6	c.-90+8017C>T		intron_variant	Intron 1 of 14	5		ENSP00000461484.1
KANSL1	ENST00000574590.6	c.-90+8017C>T		intron_variant	Intron 2 of 15	2		ENSP00000461812.2
KANSL1	ENST00000648792.1	c.-90+8017C>T		intron_variant	Intron 2 of 15			ENSP00000497628.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21963 AN: 152070 Hom.: 2139 Cov.: 35

Gnomad AFR AF: 0.0434

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0749

Gnomad FIN AF: 0.0655

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.144 AC: 21952 AN: 152188 Hom.: 2137 Cov.: 35 AF XY: 0.135 AC XY: 10042 AN XY: 74414

African (AFR) AF: 0.0433 AC: 1800 AN: 41540

American (AMR) AF: 0.178 AC: 2713 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 834 AN: 3466

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5184

South Asian (SAS) AF: 0.0750 AC: 362 AN: 4828

European-Finnish (FIN) AF: 0.0655 AC: 695 AN: 10606

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.218 AC: 14815 AN: 67974

Other (OTH) AF: 0.183 AC: 387 AN: 2110

Alfa AF: 0.186 Hom.: 5912

Bravo AF: 0.149

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.1
DANN	Benign	0.83
PhyloP100		-0.28
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: rs2668692; hg19: chr17-44293020;