rs1907724

Variant names:

• chr10-76980090-G-A
• rs1907724
• NM_001161352.2:c.2267-10023C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-76980090-G-A
• chr10-76980090-G-C
• chr10-76980090-G-T

Variant summary

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

The NM_001161352.2(KCNMA1):​c.2267-10023C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 152,006 control chromosomes in the GnomAD database, including 43,986 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 0.76 (43985 hom., cov: 32)
  • Exomes 𝑓: 0.63 (1 hom.)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.621
• Publications: 2 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-AS1 (HGNC:51213): (KCNMA1 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.2267-10023C>T		intron_variant	Intron 19 of 27	ENST00000286628.14	NP_001154824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14	c.2267-10023C>T		intron_variant	Intron 19 of 27	1	NM_001161352.2	ENSP00000286628.8

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115249 AN: 151880 Hom.: 43951 Cov.: 32

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.984

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.744

GnomAD4 exome AF: 0.625 AC: 5 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 3 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.759 AC: 115336 AN: 151998 Hom.: 43985 Cov.: 32 AF XY: 0.763 AC XY: 56652 AN XY: 74256

African (AFR) AF: 0.686 AC: 28393 AN: 41400

American (AMR) AF: 0.799 AC: 12218 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2570 AN: 3472

East Asian (EAS) AF: 0.984 AC: 5089 AN: 5174

South Asian (SAS) AF: 0.800 AC: 3845 AN: 4806

European-Finnish (FIN) AF: 0.788 AC: 8318 AN: 10560

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52443 AN: 67988

Other (OTH) AF: 0.747 AC: 1576 AN: 2110

Alfa AF: 0.760 Hom.: 65912

Bravo AF: 0.755

Asia WGS AF: 0.860 AC: 2990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.9
DANN	Benign	0.61
PhyloP100		0.62
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: rs1907724; hg19: chr10-78739848;