NM_001161352.2:c.809-137T>C

Variant names:

• chr10-77121185-A-G
• rs7907270
• NM_001161352.2:c.809-137T>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.809-137T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 686,138 control chromosomes in the GnomAD database, including 48,316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11157 hom., cov: 32)
  • Exomes 𝑓: 0.36 (37159 hom.)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.366
• 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 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=-0.71).
• BP6: Variant 10-77121185-A-G is Benign according to our data. Variant chr10-77121185-A-G is described in ClinVar as Benign. ClinVar VariationId is 1250074.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 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.809-137T>C		intron	N/A	NP_001154824.1	Q12791-1
	KCNMA1	NM_001437422.1		c.941-137T>C		intron	N/A	NP_001424351.1
	KCNMA1	NM_001161353.2		c.809-137T>C		intron	N/A	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.809-137T>C		intron	N/A	ENSP00000286628.8	Q12791-1
	KCNMA1	ENST00000626620.3	TSL:1	c.809-137T>C		intron	N/A	ENSP00000485867.1	Q12791-2
	KCNMA1	ENST00000639406.1	TSL:1	c.809-137T>C		intron	N/A	ENSP00000491732.1	B7ZMF5

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56519 AN: 151988 Hom.: 11144 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.0165

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.357 AC: 190421 AN: 534032 Hom.: 37159 AF XY: 0.359 AC XY: 103776 AN XY: 288966

African (AFR) AF: 0.414 AC: 6195 AN: 14956

American (AMR) AF: 0.210 AC: 6768 AN: 32262

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 10038 AN: 18928

East Asian (EAS) AF: 0.0175 AC: 555 AN: 31794

South Asian (SAS) AF: 0.336 AC: 19998 AN: 59528

European-Finnish (FIN) AF: 0.361 AC: 11656 AN: 32330

Middle Eastern (MID) AF: 0.443 AC: 1713 AN: 3868

European-Non Finnish (NFE) AF: 0.394 AC: 122465 AN: 310624

Other (OTH) AF: 0.371 AC: 11033 AN: 29742

GnomAD4 genome AF: 0.372 AC: 56566 AN: 152106 Hom.: 11157 Cov.: 32 AF XY: 0.364 AC XY: 27105 AN XY: 74366

African (AFR) AF: 0.409 AC: 16973 AN: 41482

American (AMR) AF: 0.288 AC: 4397 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1823 AN: 3464

East Asian (EAS) AF: 0.0166 AC: 86 AN: 5186

South Asian (SAS) AF: 0.311 AC: 1497 AN: 4814

European-Finnish (FIN) AF: 0.344 AC: 3645 AN: 10582

Middle Eastern (MID) AF: 0.449 AC: 131 AN: 292

European-Non Finnish (NFE) AF: 0.395 AC: 26852 AN: 67976

Other (OTH) AF: 0.388 AC: 819 AN: 2112

Alfa AF: 0.385 Hom.: 22287

Bravo AF: 0.367

Asia WGS AF: 0.171 AC: 595 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Benign	0.64
PhyloP100		0.37
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: rs7907270; hg19: chr10-78880943;