rs1218582

chr1-154861707-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
KCNN3	NM_002249.6	c.933+7325C>T		intron_variant		ENST00000271915.9
KCNN3	NM_001204087.2	c.933+7325C>T		intron_variant
KCNN3	NM_001365837.1	c.-7+6242C>T		intron_variant
KCNN3	NM_001365838.1	c.-7+6242C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNN3	ENST00000271915.9	c.933+7325C>T		intron_variant		1	NM_002249.6	P1
KCNN3	ENST00000358505.2	c.-7+6242C>T		intron_variant		1
KCNN3	ENST00000618040.4	c.933+7325C>T		intron_variant		5

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

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.0899

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.457

Alfa AF: 0.526 Hom.: 5152

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1218582; hg19: chr1-154834183;