rs1131824

Variant names:

• chr10-77184832-G-A
• rs1131824
• NM_001161352.2:c.687C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-77184832-G-A
• chr10-77184832-G-T
• chr10-77184832-G-C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_Strong BP7 BA1

The NM_001161352.2(KCNMA1):​c.687C>T​(p.Phe229Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 1,600,698 control chromosomes in the GnomAD database, including 108,354 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15184 hom., cov: 32)
  • Exomes 𝑓: 0.35 (93170 hom.)
• Consequence: KCNMA1 NM_001161352.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 1.40
• Publications: 25 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet, Illumina
• Liang-Wang syndrome

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

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

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP6: Variant 10-77184832-G-A is Benign according to our data. Variant chr10-77184832-G-A is described in ClinVar as Benign. ClinVar VariationId is 129328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.4 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 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.687C>T	p.Phe229Phe	synonymous	Exon 4 of 28	NP_001154824.1	Q12791-1
	KCNMA1	NM_001437422.1		c.819C>T	p.Phe273Phe	synonymous	Exon 5 of 28	NP_001424351.1
	KCNMA1	NM_001161353.2		c.687C>T	p.Phe229Phe	synonymous	Exon 4 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.687C>T	p.Phe229Phe	synonymous	Exon 4 of 28	ENSP00000286628.8	Q12791-1
	KCNMA1	ENST00000626620.3	TSL:1	c.687C>T	p.Phe229Phe	synonymous	Exon 4 of 28	ENSP00000485867.1	Q12791-2
	KCNMA1	ENST00000639406.1	TSL:1	c.687C>T	p.Phe229Phe	synonymous	Exon 4 of 29	ENSP00000491732.1	B7ZMF5

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64599 AN: 151846 Hom.: 15161 Cov.: 32

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.383

GnomAD2 exomes AF: 0.348 AC: 87164 AN: 250790 AF XY: 0.346

Gnomad AFR exome AF: 0.637

Gnomad AMR exome AF: 0.207

Gnomad ASJ exome AF: 0.404

Gnomad EAS exome AF: 0.267

Gnomad FIN exome AF: 0.371

Gnomad NFE exome AF: 0.359

Gnomad OTH exome AF: 0.337

GnomAD4 exome AF: 0.352 AC: 510383 AN: 1448734 Hom.: 93170 Cov.: 30 AF XY: 0.351 AC XY: 253401 AN XY: 721448

African (AFR) AF: 0.636 AC: 21078 AN: 33144

American (AMR) AF: 0.213 AC: 9528 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 10564 AN: 26044

East Asian (EAS) AF: 0.255 AC: 10087 AN: 39598

South Asian (SAS) AF: 0.330 AC: 28340 AN: 85980

European-Finnish (FIN) AF: 0.371 AC: 19778 AN: 53272

Middle Eastern (MID) AF: 0.410 AC: 2352 AN: 5740

European-Non Finnish (NFE) AF: 0.352 AC: 387281 AN: 1100358

Other (OTH) AF: 0.357 AC: 21375 AN: 59904

GnomAD4 genome AF: 0.425 AC: 64660 AN: 151964 Hom.: 15184 Cov.: 32 AF XY: 0.423 AC XY: 31414 AN XY: 74268

African (AFR) AF: 0.634 AC: 26273 AN: 41448

American (AMR) AF: 0.324 AC: 4943 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1418 AN: 3466

East Asian (EAS) AF: 0.260 AC: 1334 AN: 5124

South Asian (SAS) AF: 0.333 AC: 1604 AN: 4814

European-Finnish (FIN) AF: 0.386 AC: 4072 AN: 10550

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23844 AN: 67984

Other (OTH) AF: 0.379 AC: 799 AN: 2108

Alfa AF: 0.376 Hom.: 43685

Bravo AF: 0.428

Asia WGS AF: 0.313 AC: 1086 AN: 3478

EpiCase AF: 0.355

EpiControl AF: 0.359

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Generalized epilepsy-paroxysmal dyskinesia syndrome (3)
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Cerebellar atrophy, developmental delay, and seizures (1)
-	-	1	Liang-Wang syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	10
DANN	Benign	0.77
PhyloP100		1.4
PromoterAI		-0.035	Neutral
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: rs1131824; hg19: chr10-78944590; COSMIC: COSV54248693; COSMIC: COSV54248693;