rs11808053

Variant names:

• chr1-154776571-T-C
• rs11808053
• NM_002249.6:c.1030-4178A>G

Variant summary

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

The NM_002249.6(KCNN3):​c.1030-4178A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 151,968 control chromosomes in the GnomAD database, including 8,954 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 0.33 (8954 hom., cov: 31)
• Consequence: KCNN3 NM_002249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNN3	NM_002249.6	c.1030-4178A>G		intron_variant	Intron 2 of 7	ENST00000271915.9	NP_002240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNN3	ENST00000271915.9	c.1030-4178A>G		intron_variant	Intron 2 of 7	1	NM_002249.6	ENSP00000271915.3
KCNN3	ENST00000361147.8	c.115-4178A>G		intron_variant	Intron 2 of 7	1		ENSP00000354764.4
KCNN3	ENST00000358505.2	c.91-4178A>G		intron_variant	Intron 2 of 7	1		ENSP00000351295.2
KCNN3	ENST00000618040.4	c.1030-4178A>G		intron_variant	Intron 2 of 8	5		ENSP00000481848.1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50300 AN: 151848 Hom.: 8956 Cov.: 31

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.331 AC: 50308 AN: 151968 Hom.: 8954 Cov.: 31 AF XY: 0.336 AC XY: 24931 AN XY: 74264

African (AFR) AF: 0.209 AC: 8675 AN: 41436

American (AMR) AF: 0.314 AC: 4807 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1870 AN: 3470

East Asian (EAS) AF: 0.305 AC: 1568 AN: 5148

South Asian (SAS) AF: 0.369 AC: 1778 AN: 4820

European-Finnish (FIN) AF: 0.461 AC: 4870 AN: 10570

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25460 AN: 67922

Other (OTH) AF: 0.373 AC: 788 AN: 2110

Alfa AF: 0.360 Hom.: 39332

Bravo AF: 0.312

Asia WGS AF: 0.333 AC: 1159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.62
PhyloP100		0.51
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: rs11808053; hg19: chr1-154749047;