rs2288840

Variant names:

• chr10-76889641-C-T
• rs2288840
• NM_001161352.2:c.3343-72G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-76889641-C-T
• chr10-76889641-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001161352.2(KCNMA1):​c.3343-72G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 1,233,774 control chromosomes in the GnomAD database, including 275,239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31875 hom., cov: 32)
  • Exomes 𝑓: 0.67 (243364 hom.)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.773
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-76889641-C-T is Benign according to our data. Variant chr10-76889641-C-T is described in ClinVar as Benign. ClinVar VariationId is 1221813.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 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.3343-72G>A		intron	N/A	NP_001154824.1	Q12791-1
	KCNMA1	NM_001437422.1		c.3301-72G>A		intron	N/A	NP_001424351.1
	KCNMA1	NM_001161353.2		c.3292-72G>A		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.3343-72G>A		intron	N/A	ENSP00000286628.8	Q12791-1
	KCNMA1	ENST00000626620.3	TSL:1	c.3292-72G>A		intron	N/A	ENSP00000485867.1	Q12791-2
	KCNMA1	ENST00000639406.1	TSL:1	c.3259-72G>A		intron	N/A	ENSP00000491732.1	B7ZMF5

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97635 AN: 151908 Hom.: 31837 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.651

GnomAD4 exome AF: 0.667 AC: 721253 AN: 1081748 Hom.: 243364 Cov.: 15 AF XY: 0.662 AC XY: 368505 AN XY: 556420

African (AFR) AF: 0.568 AC: 14793 AN: 26046

American (AMR) AF: 0.595 AC: 26319 AN: 44248

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 15573 AN: 23754

East Asian (EAS) AF: 0.451 AC: 17091 AN: 37874

South Asian (SAS) AF: 0.530 AC: 41546 AN: 78398

European-Finnish (FIN) AF: 0.757 AC: 37934 AN: 50080

Middle Eastern (MID) AF: 0.590 AC: 2992 AN: 5072

European-Non Finnish (NFE) AF: 0.695 AC: 533620 AN: 768260

Other (OTH) AF: 0.654 AC: 31385 AN: 48016

GnomAD4 genome AF: 0.643 AC: 97720 AN: 152026 Hom.: 31875 Cov.: 32 AF XY: 0.641 AC XY: 47625 AN XY: 74304

African (AFR) AF: 0.574 AC: 23790 AN: 41418

American (AMR) AF: 0.614 AC: 9377 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2224 AN: 3470

East Asian (EAS) AF: 0.461 AC: 2383 AN: 5168

South Asian (SAS) AF: 0.520 AC: 2505 AN: 4818

European-Finnish (FIN) AF: 0.762 AC: 8071 AN: 10590

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47222 AN: 67970

Other (OTH) AF: 0.653 AC: 1377 AN: 2108

Alfa AF: 0.668 Hom.: 43041

Bravo AF: 0.630

Asia WGS AF: 0.544 AC: 1890 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.30
DANN	Benign	0.64
PhyloP100		-0.77
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: rs2288840; hg19: chr10-78649399; COSMIC: COSV107271150; COSMIC: COSV107271150;