rs11810841

Variant names:

• chr1-154738821-A-G
• rs11810841
• NM_002249.6:c.1449-5677T>C

Variant summary

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

The NM_002249.6(KCNN3):​c.1449-5677T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,226 control chromosomes in the GnomAD database, including 6,002 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 0.27 (6002 hom., cov: 33)
• Consequence: KCNN3 NM_002249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.386
• Publications: 2 publications found

Genes affected

KCNN3 (HGNC:6292): (potassium calcium-activated channel subfamily N member 3) Action potentials in vertebrate neurons are followed by an afterhyperpolarization (AHP) that may persist for several seconds and may have profound consequences for the firing pattern of the neuron. Each component of the AHP is kinetically distinct and is mediated by different calcium-activated potassium channels. This gene belongs to the KCNN family of potassium channels. It encodes an integral membrane protein that forms a voltage-independent calcium-activated channel, which is thought to regulate neuronal excitability by contributing to the slow component of synaptic AHP. This gene contains two CAG repeat regions in the coding sequence. It was thought that expansion of one or both of these repeats could lead to an increased susceptibility to schizophrenia or bipolar disorder, but studies indicate that this is probably not the case. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]

KCNN3 Gene-Disease associations (from GenCC):

• Zimmermann-Laband syndrome 3

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Zimmermann-Laband syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• schizophrenia

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNN3	NM_002249.6	c.1449-5677T>C		intron_variant	Intron 3 of 7	ENST00000271915.9	NP_002240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNN3	ENST00000271915.9	c.1449-5677T>C		intron_variant	Intron 3 of 7	1	NM_002249.6	ENSP00000271915.3
KCNN3	ENST00000361147.8	c.534-5677T>C		intron_variant	Intron 3 of 7	1		ENSP00000354764.4
KCNN3	ENST00000358505.2	c.510-5677T>C		intron_variant	Intron 3 of 7	1		ENSP00000351295.2
KCNN3	ENST00000618040.4	c.1449-1733T>C		intron_variant	Intron 3 of 8	5		ENSP00000481848.1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41524 AN: 152108 Hom.: 5995 Cov.: 33

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.273 AC: 41562 AN: 152226 Hom.: 6002 Cov.: 33 AF XY: 0.267 AC XY: 19843 AN XY: 74432

African (AFR) AF: 0.270 AC: 11203 AN: 41528

American (AMR) AF: 0.184 AC: 2819 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 932 AN: 3470

East Asian (EAS) AF: 0.0104 AC: 54 AN: 5188

South Asian (SAS) AF: 0.176 AC: 850 AN: 4822

European-Finnish (FIN) AF: 0.302 AC: 3202 AN: 10592

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21595 AN: 68004

Other (OTH) AF: 0.251 AC: 530 AN: 2114

Alfa AF: 0.300 Hom.: 11373

Bravo AF: 0.263

Asia WGS AF: 0.118 AC: 411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.40
PhyloP100		-0.39
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: rs11810841; hg19: chr1-154711297;