rs1218585

chr1-154860185-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+8847C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,236 control chromosomes in the GnomAD database, including 2,735 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 0.18 (2735 hom., cov: 32)
• Consequence: KCNN3 NM_002249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.577

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNN3	NM_002249.6	c.933+8847C>T		intron_variant		ENST00000271915.9
KCNN3	NM_001204087.2	c.933+8847C>T		intron_variant
KCNN3	NM_001365837.1	c.-7+7764C>T		intron_variant
KCNN3	NM_001365838.1	c.-7+7764C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNN3	ENST00000271915.9	c.933+8847C>T		intron_variant		1	NM_002249.6	P1
KCNN3	ENST00000358505.2	c.-7+7764C>T		intron_variant		1
KCNN3	ENST00000618040.4	c.933+8847C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27113 AN: 152118 Hom.: 2737 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.00924

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.178 AC: 27114 AN: 152236 Hom.: 2735 Cov.: 32 AF XY: 0.172 AC XY: 12840 AN XY: 74442

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.00926

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.180

Alfa AF: 0.217 Hom.: 3006

Bravo AF: 0.170

Asia WGS AF: 0.0530 AC: 187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.6
Dann	Benign	0.83

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: rs1218585; hg19: chr1-154832661;