10-77483744-G-T

Variant names:

• chr10-77483744-G-T
• rs35791
• NM_001161352.2:c.379-79721C>A

Variant summary

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

The NM_001161352.2(KCNMA1):​c.379-79721C>A variant causes a intron change. The variant allele was found at a frequency of 0.545 in 152,006 control chromosomes in the GnomAD database, including 22,791 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 0.54 (22791 hom., cov: 32)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.99
• 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.379-79721C>A		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.379-79721C>A		intron_variant	Intron 1 of 27	1	NM_001161352.2	ENSP00000286628.8

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82779 AN: 151888 Hom.: 22786 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.545 AC: 82817 AN: 152006 Hom.: 22791 Cov.: 32 AF XY: 0.551 AC XY: 40913 AN XY: 74292

African (AFR) AF: 0.519 AC: 21508 AN: 41454

American (AMR) AF: 0.579 AC: 8842 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2182 AN: 3470

East Asian (EAS) AF: 0.787 AC: 4060 AN: 5156

South Asian (SAS) AF: 0.627 AC: 3024 AN: 4822

European-Finnish (FIN) AF: 0.548 AC: 5786 AN: 10560

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35602 AN: 67960

Other (OTH) AF: 0.557 AC: 1176 AN: 2110

Alfa AF: 0.536 Hom.: 17686

Bravo AF: 0.545

Asia WGS AF: 0.686 AC: 2385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.47
PhyloP100		4.0
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: rs35791; hg19: chr10-79243502;