rs1218582

Variant names:

• chr1-154861707-G-A
• rs1218582
• NM_002249.6:c.933+7325C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-154861707-G-A
• chr1-154861707-G-C
• chr1-154861707-G-T

Variant summary

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

The NM_002249.6(KCNN3):​c.933+7325C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,964 control chromosomes in the GnomAD database, including 16,762 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 0.45 (16762 hom., cov: 32)
• Consequence: KCNN3 NM_002249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 63 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNN3	NM_002249.6	c.933+7325C>T		intron_variant	Intron 1 of 7	ENST00000271915.9	NP_002240.3
KCNN3	NM_001204087.2	c.933+7325C>T		intron_variant	Intron 1 of 8		NP_001191016.1
KCNN3	NM_001365837.1	c.-7+6242C>T		intron_variant	Intron 1 of 8		NP_001352766.1
KCNN3	NM_001365838.1	c.-7+6242C>T		intron_variant	Intron 1 of 7		NP_001352767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNN3	ENST00000271915.9	c.933+7325C>T		intron_variant	Intron 1 of 7	1	NM_002249.6	ENSP00000271915.3
KCNN3	ENST00000358505.2	c.-7+6242C>T		intron_variant	Intron 1 of 7	1		ENSP00000351295.2
KCNN3	ENST00000618040.4	c.933+7325C>T		intron_variant	Intron 1 of 8	5		ENSP00000481848.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68626 AN: 151846 Hom.: 16753 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.0897

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.452 AC: 68656 AN: 151964 Hom.: 16762 Cov.: 32 AF XY: 0.446 AC XY: 33152 AN XY: 74260

African (AFR) AF: 0.338 AC: 14008 AN: 41428

American (AMR) AF: 0.387 AC: 5909 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1524 AN: 3470

East Asian (EAS) AF: 0.0899 AC: 466 AN: 5184

South Asian (SAS) AF: 0.315 AC: 1513 AN: 4810

European-Finnish (FIN) AF: 0.576 AC: 6077 AN: 10542

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37496 AN: 67948

Other (OTH) AF: 0.457 AC: 963 AN: 2108

Alfa AF: 0.507 Hom.: 34813

Bravo AF: 0.433

Asia WGS AF: 0.223 AC: 778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.6
DANN	Benign	0.47
PhyloP100		1.3
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: rs1218582; hg19: chr1-154834183;