NM_001161352.2:c.3017-1587A>G

Variant names:

• chr10-76911683-T-C
• rs16934025
• NM_001161352.2:c.3017-1587A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001161352.2(KCNMA1):​c.3017-1587A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,114 control chromosomes in the GnomAD database, including 4,447 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4445 hom., cov: 32)
  • Exomes 𝑓: 0.24 (2 hom.)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.3017-1587A>G		intron_variant	Intron 24 of 27	ENST00000286628.14	NP_001154824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14	c.3017-1587A>G		intron_variant	Intron 24 of 27	1	NM_001161352.2	ENSP00000286628.8

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34686 AN: 151942 Hom.: 4420 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.241 AC: 13 AN: 54 Hom.: 2 Cov.: 0 AF XY: 0.225 AC XY: 9 AN XY: 40

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.200 AC: 10 AN: 50

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.229 AC: 34770 AN: 152060 Hom.: 4445 Cov.: 32 AF XY: 0.230 AC XY: 17118 AN XY: 74310

African (AFR) AF: 0.308 AC: 12750 AN: 41448

American (AMR) AF: 0.328 AC: 5004 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0968 AC: 336 AN: 3472

East Asian (EAS) AF: 0.162 AC: 836 AN: 5166

South Asian (SAS) AF: 0.124 AC: 596 AN: 4824

European-Finnish (FIN) AF: 0.222 AC: 2345 AN: 10574

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12244 AN: 67990

Other (OTH) AF: 0.189 AC: 399 AN: 2110

Alfa AF: 0.203 Hom.: 689

Bravo AF: 0.241

Asia WGS AF: 0.233 AC: 811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.58
DANN	Benign	0.64
PhyloP100		-1.1
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: rs16934025; hg19: chr10-78671441;