10-76977837-T-C

Variant names:

• chr10-76977837-T-C
• rs16934131
• NM_001161352.2:c.2267-7770A>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.2267-7770A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 570,690 control chromosomes in the GnomAD database, including 18,017 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 (4308 hom., cov: 32)
  • Exomes 𝑓: 0.24 (13709 hom.)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546
• Publications: 11 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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMA1	NM_001161352.2	MANE Select	c.2267-7770A>G		intron	N/A	NP_001154824.1
	KCNMA1	NM_001437422.1		c.2225-7770A>G		intron	N/A	NP_001424351.1
	KCNMA1	NM_001161353.2		c.2093-7770A>G		intron	N/A	NP_001154825.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMA1	ENST00000286628.14	TSL:1 MANE Select	c.2267-7770A>G		intron	N/A	ENSP00000286628.8
	KCNMA1	ENST00000626620.3	TSL:1	c.2093-7770A>G		intron	N/A	ENSP00000485867.1
	KCNMA1	ENST00000639406.1	TSL:1	c.2102-7770A>G		intron	N/A	ENSP00000491732.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34593 AN: 151928 Hom.: 4312 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0256

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.242 AC: 101487 AN: 418644 Hom.: 13709 Cov.: 0 AF XY: 0.244 AC XY: 53581 AN XY: 219834

African (AFR) AF: 0.168 AC: 2004 AN: 11932

American (AMR) AF: 0.148 AC: 2622 AN: 17678

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 2381 AN: 13080

East Asian (EAS) AF: 0.0233 AC: 688 AN: 29582

South Asian (SAS) AF: 0.259 AC: 10375 AN: 40130

European-Finnish (FIN) AF: 0.342 AC: 9413 AN: 27556

Middle Eastern (MID) AF: 0.239 AC: 449 AN: 1878

European-Non Finnish (NFE) AF: 0.268 AC: 67670 AN: 252226

Other (OTH) AF: 0.239 AC: 5885 AN: 24582

GnomAD4 genome AF: 0.228 AC: 34593 AN: 152046 Hom.: 4308 Cov.: 32 AF XY: 0.229 AC XY: 16987 AN XY: 74302

African (AFR) AF: 0.166 AC: 6865 AN: 41474

American (AMR) AF: 0.186 AC: 2835 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 669 AN: 3468

East Asian (EAS) AF: 0.0255 AC: 132 AN: 5178

South Asian (SAS) AF: 0.257 AC: 1240 AN: 4824

European-Finnish (FIN) AF: 0.359 AC: 3787 AN: 10548

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18120 AN: 67974

Other (OTH) AF: 0.216 AC: 456 AN: 2108

Alfa AF: 0.246 Hom.: 18306

Bravo AF: 0.208

Asia WGS AF: 0.150 AC: 524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.1
DANN	Benign	0.66
PhyloP100		0.55
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: rs16934131; hg19: chr10-78737595;