rs1881194

Variant names:

• chr17-46171448-G-A
• rs1881194
• NM_015443.4:c.696C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015443.4(KANSL1):​c.696C>T​(p.Ser232Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,613,058 control chromosomes in the GnomAD database, including 32,760 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2135 hom., cov: 35)
  • Exomes 𝑓: 0.19 (30625 hom.)
• Consequence: KANSL1 NM_015443.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.98
• Publications: 32 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 17-46171448-G-A is Benign according to our data. Variant chr17-46171448-G-A is described in ClinVar as Benign. ClinVar VariationId is 323789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.98 with no splicing effect.
• 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_015443.4	c.696C>T	p.Ser232Ser	synonymous_variant	Exon 2 of 15	ENST00000432791.7	NP_056258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANSL1	ENST00000432791.7	c.696C>T	p.Ser232Ser	synonymous_variant	Exon 2 of 15	1	NM_015443.4	ENSP00000387393.3

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21945 AN: 151946 Hom.: 2137 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: 0.0744

Gnomad FIN AF: 0.0658

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.186

GnomAD2 exomes AF: 0.146 AC: 36664 AN: 251178 AF XY: 0.149

Gnomad AFR exome AF: 0.0401

Gnomad AMR exome AF: 0.120

Gnomad ASJ exome AF: 0.254

Gnomad EAS exome AF: 0.000707

Gnomad FIN exome AF: 0.0689

Gnomad NFE exome AF: 0.215

Gnomad OTH exome AF: 0.176

GnomAD4 exome AF: 0.194 AC: 283787 AN: 1460994 Hom.: 30625 Cov.: 50 AF XY: 0.192 AC XY: 139391 AN XY: 726812

African (AFR) AF: 0.0369 AC: 1234 AN: 33478

American (AMR) AF: 0.126 AC: 5639 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 6713 AN: 26110

East Asian (EAS) AF: 0.000907 AC: 36 AN: 39698

South Asian (SAS) AF: 0.0797 AC: 6874 AN: 86200

European-Finnish (FIN) AF: 0.0731 AC: 3904 AN: 53404

Middle Eastern (MID) AF: 0.203 AC: 1169 AN: 5768

European-Non Finnish (NFE) AF: 0.223 AC: 247489 AN: 1111260

Other (OTH) AF: 0.178 AC: 10729 AN: 60370

GnomAD4 genome AF: 0.144 AC: 21934 AN: 152064 Hom.: 2135 Cov.: 35 AF XY: 0.135 AC XY: 10028 AN XY: 74320

African (AFR) AF: 0.0433 AC: 1797 AN: 41466

American (AMR) AF: 0.177 AC: 2706 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3472

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5172

South Asian (SAS) AF: 0.0745 AC: 359 AN: 4820

European-Finnish (FIN) AF: 0.0658 AC: 697 AN: 10590

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14806 AN: 67974

Other (OTH) AF: 0.183 AC: 387 AN: 2112

Alfa AF: 0.196 Hom.: 3826

Bravo AF: 0.149

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 20, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Koolen-de Vries syndrome Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	9.6
DANN	Benign	0.69
PhyloP100		3.0
PromoterAI		-0.026	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=273/27	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: rs1881194; hg19: chr17-44248814;