rs2838

Variant names:

• chr17-46063981-A-G
• rs2838
• NM_015443.4:c.1848+2556T>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.1848+2556T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 147,896 control chromosomes in the GnomAD database, including 2,080 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 (2080 hom., cov: 25)
• Consequence: KANSL1 NM_015443.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.950
• Publications: 21 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANSL1	NM_015443.4	c.1848+2556T>C		intron_variant	Intron 6 of 14	ENST00000432791.7	NP_056258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANSL1	ENST00000432791.7	c.1848+2556T>C		intron_variant	Intron 6 of 14	1	NM_015443.4	ENSP00000387393.3

Frequencies

GnomAD3 genomes AF: 0.142 AC: 20966 AN: 147806 Hom.: 2082 Cov.: 25

Gnomad AFR AF: 0.0412

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.00156

Gnomad SAS AF: 0.0729

Gnomad FIN AF: 0.0473

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.142 AC: 20950 AN: 147896 Hom.: 2080 Cov.: 25 AF XY: 0.132 AC XY: 9494 AN XY: 72088

African (AFR) AF: 0.0411 AC: 1665 AN: 40506

American (AMR) AF: 0.171 AC: 2520 AN: 14740

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 833 AN: 3458

East Asian (EAS) AF: 0.00156 AC: 8 AN: 5112

South Asian (SAS) AF: 0.0729 AC: 343 AN: 4706

European-Finnish (FIN) AF: 0.0473 AC: 429 AN: 9066

Middle Eastern (MID) AF: 0.214 AC: 62 AN: 290

European-Non Finnish (NFE) AF: 0.216 AC: 14473 AN: 67084

Other (OTH) AF: 0.180 AC: 365 AN: 2028

Alfa AF: 0.196 Hom.: 1320

Bravo AF: 0.148

Asia WGS AF: 0.0300 AC: 104 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	10
DANN	Benign	0.79
PhyloP100		0.95
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: rs2838; hg19: chr17-44141347;