rs45586138

Variant names:

• chr10-76891627-G-A
• rs45586138
• NM_001161352.2:c.3240C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-76891627-G-A
• chr10-76891627-G-C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_Strong BP7 BS1 BS2

The NM_001161352.2(KCNMA1):​c.3240C>T​(p.Asn1080Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00439 in 1,614,054 control chromosomes in the GnomAD database, including 32 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0045 (32 hom.)
• Consequence: KCNMA1 NM_001161352.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.269
• Publications: 1 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 -17 ACMG points.

• BP6: Variant 10-76891627-G-A is Benign according to our data. Variant chr10-76891627-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 284179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.269 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00362 (551/152308) while in subpopulation AMR AF = 0.00771 (118/15302). AF 95% confidence interval is 0.00658. There are 0 homozygotes in GnomAd4. There are 262 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 32 AD,AR gene

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.3240C>T	p.Asn1080Asn	synonymous	Exon 26 of 28	NP_001154824.1	Q12791-1
	KCNMA1	NM_001437422.1		c.3198C>T	p.Asn1066Asn	synonymous	Exon 26 of 28	NP_001424351.1
	KCNMA1	NM_001161353.2		c.3189C>T	p.Asn1063Asn	synonymous	Exon 26 of 28	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.3240C>T	p.Asn1080Asn	synonymous	Exon 26 of 28	ENSP00000286628.8	Q12791-1
	KCNMA1	ENST00000626620.3	TSL:1	c.3189C>T	p.Asn1063Asn	synonymous	Exon 26 of 28	ENSP00000485867.1	Q12791-2
	KCNMA1	ENST00000639406.1	TSL:1	c.3156C>T	p.Asn1052Asn	synonymous	Exon 27 of 29	ENSP00000491732.1	B7ZMF5

Frequencies

GnomAD3 genomes AF: 0.00363 AC: 552 AN: 152190 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00456

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.00347 AC: 871 AN: 251002 AF XY: 0.00342

Gnomad AFR exome AF: 0.00135

Gnomad AMR exome AF: 0.00564

Gnomad ASJ exome AF: 0.00278

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00246

Gnomad NFE exome AF: 0.00461

Gnomad OTH exome AF: 0.00588

GnomAD4 exome AF: 0.00447 AC: 6533 AN: 1461746 Hom.: 32 Cov.: 31 AF XY: 0.00441 AC XY: 3204 AN XY: 727184

African (AFR) AF: 0.000896 AC: 30 AN: 33478

American (AMR) AF: 0.00606 AC: 271 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00295 AC: 77 AN: 26136

East Asian (EAS) AF: 0.00136 AC: 54 AN: 39700

South Asian (SAS) AF: 0.000568 AC: 49 AN: 86258

European-Finnish (FIN) AF: 0.00238 AC: 127 AN: 53324

Middle Eastern (MID) AF: 0.00277 AC: 16 AN: 5768

European-Non Finnish (NFE) AF: 0.00508 AC: 5648 AN: 1111968

Other (OTH) AF: 0.00432 AC: 261 AN: 60394

GnomAD4 genome AF: 0.00362 AC: 551 AN: 152308 Hom.: 0 Cov.: 33 AF XY: 0.00352 AC XY: 262 AN XY: 74476

African (AFR) AF: 0.00135 AC: 56 AN: 41582

American (AMR) AF: 0.00771 AC: 118 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.000774 AC: 4 AN: 5166

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00320 AC: 34 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00454 AC: 309 AN: 68020

Other (OTH) AF: 0.00851 AC: 18 AN: 2116

Alfa AF: 0.00389 Hom.: 0

Bravo AF: 0.00431

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00491

EpiControl AF: 0.00528

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	2	Generalized epilepsy-paroxysmal dyskinesia syndrome (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	1.5
DANN	Benign	0.88
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism

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: rs45586138; hg19: chr10-78651385;