rs2116830

Variant names:

• chr10-76886778-G-T
• rs2116830
• NM_001161352.2:c.*488C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-76886778-G-T
• chr10-76886778-G-C

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.*488C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,025,966 control chromosomes in the GnomAD database, including 18,376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1789 hom., cov: 33)
  • Exomes 𝑓: 0.19 (16587 hom.)
• Consequence: KCNMA1 NM_001161352.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.891
• Publications: 39 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 10-76886778-G-T is Benign according to our data. Variant chr10-76886778-G-T is described in ClinVar as Benign. ClinVar VariationId is 300951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.193 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.*488C>A		3_prime_UTR	Exon 28 of 28	NP_001154824.1	Q12791-1
	KCNMA1	NM_001437422.1		c.*488C>A		3_prime_UTR	Exon 28 of 28	NP_001424351.1
	KCNMA1	NM_001161353.2		c.*488C>A		3_prime_UTR	Exon 28 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.*488C>A		3_prime_UTR	Exon 28 of 28	ENSP00000286628.8	Q12791-1
	KCNMA1	ENST00000639406.1	TSL:1	c.*488C>A		3_prime_UTR	Exon 29 of 29	ENSP00000491732.1	B7ZMF5
	KCNMA1	ENST00000286627.10	TSL:1	c.*488C>A		3_prime_UTR	Exon 27 of 27	ENSP00000286627.5	Q12791-5

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20654 AN: 152050 Hom.: 1789 Cov.: 33

Gnomad AFR AF: 0.0526

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0432

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.176

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.191 AC: 166525 AN: 873796 Hom.: 16587 Cov.: 32 AF XY: 0.190 AC XY: 77354 AN XY: 406118

African (AFR) AF: 0.0370 AC: 616 AN: 16650

American (AMR) AF: 0.122 AC: 537 AN: 4412

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 834 AN: 5976

East Asian (EAS) AF: 0.000626 AC: 4 AN: 6394

South Asian (SAS) AF: 0.0425 AC: 944 AN: 22226

European-Finnish (FIN) AF: 0.133 AC: 229 AN: 1722

Middle Eastern (MID) AF: 0.122 AC: 211 AN: 1734

European-Non Finnish (NFE) AF: 0.201 AC: 158249 AN: 785422

Other (OTH) AF: 0.167 AC: 4901 AN: 29260

GnomAD4 genome AF: 0.136 AC: 20646 AN: 152170 Hom.: 1789 Cov.: 33 AF XY: 0.131 AC XY: 9742 AN XY: 74392

African (AFR) AF: 0.0524 AC: 2174 AN: 41528

American (AMR) AF: 0.155 AC: 2366 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 518 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5170

South Asian (SAS) AF: 0.0436 AC: 210 AN: 4818

European-Finnish (FIN) AF: 0.149 AC: 1580 AN: 10578

Middle Eastern (MID) AF: 0.186 AC: 54 AN: 290

European-Non Finnish (NFE) AF: 0.195 AC: 13287 AN: 67998

Other (OTH) AF: 0.166 AC: 351 AN: 2112

Alfa AF: 0.169 Hom.: 7670

Bravo AF: 0.134

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Generalized epilepsy-paroxysmal dyskinesia syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.7
DANN	Benign	0.51
PhyloP100		0.89
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: rs2116830; hg19: chr10-78646536;