rs2917454

Variant names:

• chr10-77132657-T-C
• rs2917454
• NM_001161352.2:c.809-11609A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-77132657-T-C
• chr10-77132657-T-G

Variant summary

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

The NM_001161352.2(KCNMA1):​c.809-11609A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 151,892 control chromosomes in the GnomAD database, including 3,765 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 0.15 (3765 hom., cov: 31)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161352.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMA1	NM_001161352.2	MANE Select	c.809-11609A>G		intron	N/A	NP_001154824.1
	KCNMA1	NM_001437422.1		c.941-11609A>G		intron	N/A	NP_001424351.1
	KCNMA1	NM_001161353.2		c.809-11609A>G		intron	N/A	NP_001154825.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMA1	ENST00000286628.14	TSL:1 MANE Select	c.809-11609A>G		intron	N/A	ENSP00000286628.8
	KCNMA1	ENST00000626620.3	TSL:1	c.809-11609A>G		intron	N/A	ENSP00000485867.1
	KCNMA1	ENST00000639406.1	TSL:1	c.809-11609A>G		intron	N/A	ENSP00000491732.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23173 AN: 151778 Hom.: 3750 Cov.: 31

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.0969

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.0997

Gnomad MID AF: 0.0737

Gnomad NFE AF: 0.0532

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.153 AC: 23206 AN: 151892 Hom.: 3765 Cov.: 31 AF XY: 0.163 AC XY: 12078 AN XY: 74210

African (AFR) AF: 0.202 AC: 8343 AN: 41404

American (AMR) AF: 0.233 AC: 3554 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0392 AC: 136 AN: 3472

East Asian (EAS) AF: 0.870 AC: 4473 AN: 5144

South Asian (SAS) AF: 0.337 AC: 1626 AN: 4818

European-Finnish (FIN) AF: 0.0997 AC: 1047 AN: 10506

Middle Eastern (MID) AF: 0.0759 AC: 22 AN: 290

European-Non Finnish (NFE) AF: 0.0532 AC: 3616 AN: 67986

Other (OTH) AF: 0.142 AC: 301 AN: 2114

Alfa AF: 0.0937 Hom.: 7337

Bravo AF: 0.165

Asia WGS AF: 0.548 AC: 1905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.33
PhyloP100		-0.14
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: rs2917454; hg19: chr10-78892415;