rs11808053

Positions:

• chr1-154776571-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.84).
• 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/exons	MANE	Protein	UniProt
KCNN3	NM_002249.6	c.1030-4178A>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.1030-4178A>G		intron_variant		1	NM_002249.6	ENSP00000271915	P1
KCNN3	ENST00000358505.2	c.91-4178A>G		intron_variant		1		ENSP00000351295
KCNN3	ENST00000361147.8	c.115-4178A>G		intron_variant		1		ENSP00000354764
KCNN3	ENST00000618040.4	c.1030-4178A>G		intron_variant		5		ENSP00000481848

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

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.373

Alfa AF: 0.372 Hom.: 18700

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

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: rs11808053; hg19: chr1-154749047;