chr10-76885527-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001161352.2(KCNMA1):​c.*1739G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000755 in 985,128 control chromosomes in the GnomAD database, including 5 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 0.0032 ( 3 hom., cov: 31)
Exomes 𝑓: 0.00030 ( 2 hom. )

Consequence

KCNMA1
NM_001161352.2 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.25
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00325 (494/152050) while in subpopulation AFR AF= 0.0111 (461/41444). AF 95% confidence interval is 0.0103. There are 3 homozygotes in gnomad4. There are 229 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KCNMA1NM_001161352.2 linkc.*1739G>A 3_prime_UTR_variant Exon 28 of 28 ENST00000286628.14 NP_001154824.1 Q12791-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KCNMA1ENST00000286628 linkc.*1739G>A 3_prime_UTR_variant Exon 28 of 28 1 NM_001161352.2 ENSP00000286628.8 Q12791-1

Frequencies

GnomAD3 genomes
AF:
0.00325
AC:
494
AN:
151936
Hom.:
3
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0112
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00151
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.000957
GnomAD4 exome
AF:
0.000300
AC:
250
AN:
833078
Hom.:
2
Cov.:
30
AF XY:
0.000260
AC XY:
100
AN XY:
384700
show subpopulations
Gnomad4 AFR exome
AF:
0.0126
Gnomad4 AMR exome
AF:
0.00203
Gnomad4 ASJ exome
AF:
0.000194
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000551
Gnomad4 OTH exome
AF:
0.000220
GnomAD4 genome
AF:
0.00325
AC:
494
AN:
152050
Hom.:
3
Cov.:
31
AF XY:
0.00308
AC XY:
229
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.0111
Gnomad4 AMR
AF:
0.00151
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.000732
Hom.:
1
Bravo
AF:
0.00382
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
2.4
DANN
Benign
0.68

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: rs184468198; hg19: chr10-78645285; API