rs752372

Variant names:

• chr10-77519074-A-C
• rs752372
• NM_001161352.2:c.379-115051T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-77519074-A-C
• chr10-77519074-A-G
• chr10-77519074-A-T

Variant summary

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

The NM_001161352.2(KCNMA1):​c.379-115051T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 152,144 control chromosomes in the GnomAD database, including 28,942 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 0.61 (28942 hom., cov: 34)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162
• Publications: 7 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: Illumina, G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
• Liang-Wang syndrome

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

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

LOC124902464 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.379-115051T>G		intron_variant	Intron 1 of 27	ENST00000286628.14	NP_001154824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14	c.379-115051T>G		intron_variant	Intron 1 of 27	1	NM_001161352.2	ENSP00000286628.8

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92326 AN: 152026 Hom.: 28891 Cov.: 34

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.605

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.607 AC: 92423 AN: 152144 Hom.: 28942 Cov.: 34 AF XY: 0.610 AC XY: 45365 AN XY: 74392

African (AFR) AF: 0.751 AC: 31168 AN: 41516

American (AMR) AF: 0.592 AC: 9045 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2244 AN: 3468

East Asian (EAS) AF: 0.790 AC: 4084 AN: 5172

South Asian (SAS) AF: 0.587 AC: 2831 AN: 4820

European-Finnish (FIN) AF: 0.565 AC: 5973 AN: 10578

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35147 AN: 67982

Other (OTH) AF: 0.605 AC: 1278 AN: 2114

Alfa AF: 0.547 Hom.: 28782

Bravo AF: 0.616

Asia WGS AF: 0.682 AC: 2370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	11
DANN	Benign	0.51
PhyloP100		-0.16
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: rs752372; hg19: chr10-79278832;