10-76935207-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001161352.2(KCNMA1):​c.2902+9566C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,122 control chromosomes in the GnomAD database, including 7,608 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 0.27 ( 7608 hom., cov: 33)

Consequence

KCNMA1
NM_001161352.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.681
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KCNMA1NM_001161352.2 linkuse as main transcriptc.2902+9566C>T intron_variant ENST00000286628.14 NP_001154824.1
KCNMA1-AS1NR_120655.1 linkuse as main transcriptn.457+33185G>A intron_variant, non_coding_transcript_variant
LOC124902466XR_007062207.1 linkuse as main transcriptn.275-4471G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KCNMA1ENST00000286628.14 linkuse as main transcriptc.2902+9566C>T intron_variant 1 NM_001161352.2 ENSP00000286628 A2Q12791-1
KCNMA1-AS1ENST00000458661.6 linkuse as main transcriptn.425+33185G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.272
AC:
41316
AN:
152004
Hom.:
7598
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.521
Gnomad AMI
AF:
0.242
Gnomad AMR
AF:
0.245
Gnomad ASJ
AF:
0.118
Gnomad EAS
AF:
0.130
Gnomad SAS
AF:
0.0891
Gnomad FIN
AF:
0.207
Gnomad MID
AF:
0.136
Gnomad NFE
AF:
0.171
Gnomad OTH
AF:
0.219
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.272
AC:
41372
AN:
152122
Hom.:
7608
Cov.:
33
AF XY:
0.267
AC XY:
19862
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.520
Gnomad4 AMR
AF:
0.245
Gnomad4 ASJ
AF:
0.118
Gnomad4 EAS
AF:
0.130
Gnomad4 SAS
AF:
0.0890
Gnomad4 FIN
AF:
0.207
Gnomad4 NFE
AF:
0.171
Gnomad4 OTH
AF:
0.218
Alfa
AF:
0.179
Hom.:
3802
Bravo
AF:
0.287
Asia WGS
AF:
0.150
AC:
521
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.49
DANN
Benign
0.51

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2131218; hg19: chr10-78694965; API