NM_001161352.2:c.3461+237C>T

Variant names:

• chr10-76889214-G-A
• rs11001919
• NM_001161352.2:c.3461+237C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001161352.2(KCNMA1):​c.3461+237C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,182 control chromosomes in the GnomAD database, including 2,164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2164 hom., cov: 33)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.699
• Publications: 6 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-AS1 (HGNC:51213): (KCNMA1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 10-76889214-G-A is Benign according to our data. Variant chr10-76889214-G-A is described in ClinVar as Benign. ClinVar VariationId is 1227560.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.192 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMA1	NM_001161352.2	MANE Select	c.3461+237C>T		intron	N/A	NP_001154824.1	Q12791-1
	KCNMA1	NM_001437422.1		c.3419+237C>T		intron	N/A	NP_001424351.1
	KCNMA1	NM_001161353.2		c.3410+237C>T		intron	N/A	NP_001154825.1	Q12791-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMA1	ENST00000286628.14	TSL:1 MANE Select	c.3461+237C>T		intron	N/A	ENSP00000286628.8	Q12791-1
	KCNMA1	ENST00000626620.3	TSL:1	c.3410+237C>T		intron	N/A	ENSP00000485867.1	Q12791-2
	KCNMA1	ENST00000639406.1	TSL:1	c.3377+237C>T		intron	N/A	ENSP00000491732.1	B7ZMF5

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24183 AN: 152062 Hom.: 2165 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0607

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.159 AC: 24181 AN: 152182 Hom.: 2164 Cov.: 33 AF XY: 0.154 AC XY: 11436 AN XY: 74384

African (AFR) AF: 0.130 AC: 5415 AN: 41526

American (AMR) AF: 0.166 AC: 2543 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 522 AN: 3468

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5194

South Asian (SAS) AF: 0.0610 AC: 294 AN: 4822

European-Finnish (FIN) AF: 0.149 AC: 1574 AN: 10568

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13264 AN: 68000

Other (OTH) AF: 0.187 AC: 394 AN: 2112

Alfa AF: 0.181 Hom.: 4617

Bravo AF: 0.159

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.75
PhyloP100		0.70
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: rs11001919; hg19: chr10-78648972;