chr10-77139646-C-T

Variant names:

• chr10-77139646-C-T
• rs1871063
• NM_001161352.2:c.809-18598G>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.809-18598G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,172 control chromosomes in the GnomAD database, including 3,768 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 0.15 (3768 hom., cov: 32)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.809-18598G>A		intron_variant	Intron 5 of 27	ENST00000286628.14	NP_001154824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14	c.809-18598G>A		intron_variant	Intron 5 of 27	1	NM_001161352.2	ENSP00000286628.8

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23087 AN: 152054 Hom.: 3752 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.0989

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0520

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.152 AC: 23121 AN: 152172 Hom.: 3768 Cov.: 32 AF XY: 0.162 AC XY: 12064 AN XY: 74386

African (AFR) AF: 0.201 AC: 8340 AN: 41488

American (AMR) AF: 0.232 AC: 3544 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 125 AN: 3468

East Asian (EAS) AF: 0.869 AC: 4491 AN: 5168

South Asian (SAS) AF: 0.337 AC: 1626 AN: 4826

European-Finnish (FIN) AF: 0.0989 AC: 1049 AN: 10604

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0520 AC: 3536 AN: 68022

Other (OTH) AF: 0.142 AC: 300 AN: 2114

Alfa AF: 0.123 Hom.: 365

Bravo AF: 0.164

Asia WGS AF: 0.547 AC: 1902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.0
DANN	Benign	0.45
PhyloP100		-0.36
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: rs1871063; hg19: chr10-78899404;