1-154783367-C-T

Position:

• chr1-154783367-C-T

Variant summary

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

The NM_002249.6(KCNN3):​c.1030-10974G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,106 control chromosomes in the GnomAD database, including 10,248 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 0.36 (10248 hom., cov: 32)
• Consequence: KCNN3 NM_002249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.873

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNN3	NM_002249.6	c.1030-10974G>A		intron_variant		ENST00000271915.9	NP_002240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNN3	ENST00000271915.9	c.1030-10974G>A		intron_variant		1	NM_002249.6	ENSP00000271915	P1
KCNN3	ENST00000358505.2	c.91-10974G>A		intron_variant		1		ENSP00000351295
KCNN3	ENST00000361147.8	c.115-10974G>A		intron_variant		1		ENSP00000354764
KCNN3	ENST00000618040.4	c.1030-10974G>A		intron_variant		5		ENSP00000481848

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54519 AN: 151988 Hom.: 10244 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.358 AC: 54530 AN: 152106 Hom.: 10248 Cov.: 32 AF XY: 0.364 AC XY: 27074 AN XY: 74334

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.384

Alfa AF: 0.381 Hom.: 15562

Bravo AF: 0.340

Asia WGS AF: 0.348 AC: 1212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.30
DANN	Benign	0.57

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: rs11589855; hg19: chr1-154755843;