rs1061122

Positions:

• chr1-154859814-C-T

Variant summary

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

The ENST00000271915.9(KCNN3):​c.933+9218G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,612,166 control chromosomes in the GnomAD database, including 42,768 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 0.27 (6422 hom., cov: 33)
  • Exomes 𝑓: 0.21 (36346 hom.)
• Consequence: KCNN3 ENST00000271915.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.39

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 (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNN3	NM_002249.6	c.933+9218G>A		intron_variant		ENST00000271915.9	NP_002240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNN3	ENST00000361147.8	c.-102G>A		5_prime_UTR_variant	1/8	1		ENSP00000354764
KCNN3	ENST00000271915.9	c.933+9218G>A		intron_variant		1	NM_002249.6	ENSP00000271915	P1
KCNN3	ENST00000358505.2	c.-7+8135G>A		intron_variant		1		ENSP00000351295
KCNN3	ENST00000618040.4	c.933+9218G>A		intron_variant		5		ENSP00000481848

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40720 AN: 152052 Hom.: 6418 Cov.: 33

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.00923

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.214 AC: 313144 AN: 1459996 Hom.: 36346 Cov.: 32 AF XY: 0.212 AC XY: 153926 AN XY: 726312

Gnomad4 AFR exome AF: 0.436

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.254

Gnomad4 EAS exome AF: 0.00552

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.198

Gnomad4 NFE exome AF: 0.225

Gnomad4 OTH exome AF: 0.214

GnomAD4 genome AF: 0.268 AC: 40745 AN: 152170 Hom.: 6422 Cov.: 33 AF XY: 0.259 AC XY: 19252 AN XY: 74422

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.00963

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.238

Alfa AF: 0.230 Hom.: 8847

Bravo AF: 0.273

Asia WGS AF: 0.0710 AC: 251 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	0.012
DANN	Benign	0.65

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: rs1061122; hg19: chr1-154832290; COSMIC: COSV55215271;