rs1247755

Variant names:

• chr10-77037912-C-G
• rs1247755
• NM_001161352.2:c.1859+1616G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-77037912-C-G
• chr10-77037912-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001161352.2(KCNMA1):​c.1859+1616G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 151,994 control chromosomes in the GnomAD database, including 37,323 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 0.70 (37323 hom., cov: 31)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389
• Publications: 3 publications found

Genes affected

KCNMA1 (HGNC:6284): (potassium calcium-activated channel subfamily M alpha 1) This gene encodes the alpha subunit of calcium-activated BK channel. The encoded protein is involved in several physiological processes including smooth muscle contraction, neurotransmitter release and neuronal excitability. Mutations in this gene are associated with a spectrum of neurological disorders including Paroxysmal Nonkinesigenic Dyskinesia 3, Idiopathic Generalized Epilepsy 16 and Liang-Wang syndrome. [provided by RefSeq, Aug 2022]

KCNMA1 Gene-Disease associations (from GenCC):

• generalized epilepsy-paroxysmal dyskinesia syndrome

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Illumina, G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
• Liang-Wang syndrome

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• cerebellar atrophy, developmental delay, and seizures

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.1859+1616G>C		intron_variant	Intron 15 of 27	ENST00000286628.14	NP_001154824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14	c.1859+1616G>C		intron_variant	Intron 15 of 27	1	NM_001161352.2	ENSP00000286628.8

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106438 AN: 151876 Hom.: 37285 Cov.: 31

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.700

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

GnomAD4 genome AF: 0.701 AC: 106533 AN: 151994 Hom.: 37323 Cov.: 31 AF XY: 0.701 AC XY: 52094 AN XY: 74284

African (AFR) AF: 0.710 AC: 29446 AN: 41464

American (AMR) AF: 0.746 AC: 11391 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2694 AN: 3470

East Asian (EAS) AF: 0.819 AC: 4213 AN: 5146

South Asian (SAS) AF: 0.731 AC: 3527 AN: 4822

European-Finnish (FIN) AF: 0.647 AC: 6837 AN: 10560

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46281 AN: 67960

Other (OTH) AF: 0.702 AC: 1478 AN: 2104

Alfa AF: 0.693 Hom.: 4560

Bravo AF: 0.706

Asia WGS AF: 0.748 AC: 2603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Benign	0.77
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1247755; hg19: chr10-78797670;