rs1218602

Positions:

• chr1-154818846-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002249.6(KCNN3):​c.1029+3243C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,234 control chromosomes in the GnomAD database, including 4,083 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 0.21 (4083 hom., cov: 33)
• Consequence: KCNN3 NM_002249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.612

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNN3	NM_002249.6	c.1029+3243C>G		intron_variant		ENST00000271915.9	NP_002240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNN3	ENST00000271915.9	c.1029+3243C>G		intron_variant		1	NM_002249.6	ENSP00000271915	P1
KCNN3	ENST00000358505.2	c.90+3243C>G		intron_variant		1		ENSP00000351295
KCNN3	ENST00000361147.8	c.114+3243C>G		intron_variant		1		ENSP00000354764
KCNN3	ENST00000618040.4	c.1029+3243C>G		intron_variant		5		ENSP00000481848

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32724 AN: 152116 Hom.: 4086 Cov.: 33

Gnomad AFR AF: 0.0987

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.0812

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.215 AC: 32720 AN: 152234 Hom.: 4083 Cov.: 33 AF XY: 0.218 AC XY: 16229 AN XY: 74430

Gnomad4 AFR AF: 0.0985

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.0816

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.238

Alfa AF: 0.249 Hom.: 623

Bravo AF: 0.197

Asia WGS AF: 0.182 AC: 634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.48

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: rs1218602; hg19: chr1-154791322;