rs7087337

Positions:

• chr10-76892038-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001161352.2(KCNMA1):​c.3148-319T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,106 control chromosomes in the GnomAD database, including 1,205 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 0.11 (1205 hom., cov: 32)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115

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)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNMA1	NM_001161352.2	c.3148-319T>G		intron_variant		ENST00000286628.14
KCNMA1-AS1	NR_120655.1	n.238+3757A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNMA1	ENST00000286628.14	c.3148-319T>G		intron_variant		1	NM_001161352.2	A2
KCNMA1-AS1	ENST00000458661.6	n.206+3757A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16233 AN: 151988 Hom.: 1202 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0798

Gnomad ASJ AF: 0.0885

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0807

Gnomad FIN AF: 0.0765

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0639

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.107 AC: 16250 AN: 152106 Hom.: 1205 Cov.: 32 AF XY: 0.106 AC XY: 7914 AN XY: 74348

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.0797

Gnomad4 ASJ AF: 0.0885

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0807

Gnomad4 FIN AF: 0.0765

Gnomad4 NFE AF: 0.0639

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0751 Hom.: 637

Bravo AF: 0.112

Asia WGS AF: 0.0660 AC: 228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.44

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

Other links and lift over

dbSNP: rs7087337; hg19: chr10-78651796;