10-76944983-GA-GAA

Position:

• chr10-76944983-GA-GAA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001161352.2(KCNMA1):​c.2710-19_2710-18insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00476 in 1,529,182 control chromosomes in the GnomAD database, including 40 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0099 (18 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (22 hom.)
• Consequence: KCNMA1 NM_001161352.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.262

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)

LOC124902466 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 10-76944983-G-GA is Benign according to our data. Variant chr10-76944983-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 445800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00993 (1479/148974) while in subpopulation AFR AF= 0.0333 (1350/40570). AF 95% confidence interval is 0.0318. There are 18 homozygotes in gnomad4. There are 714 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 18 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNMA1	NM_001161352.2	c.2710-19_2710-18insT		intron_variant		ENST00000286628.14
KCNMA1-AS1	NR_120655.1	n.458-32618dup		intron_variant, non_coding_transcript_variant
LOC124902466	XR_007062207.1	n.381-3974dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNMA1	ENST00000286628.14	c.2710-19_2710-18insT		intron_variant		1	NM_001161352.2	A2
KCNMA1-AS1	ENST00000458661.6	n.426-32618dup		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00994 AC: 1479 AN: 148864 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0333

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00307

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000406

Gnomad MID AF: 0.00968

Gnomad NFE AF: 0.000924

Gnomad OTH AF: 0.00688

GnomAD4 exome AF: 0.00420 AC: 5796 AN: 1380208 Hom.: 22 Cov.: 30 AF XY: 0.00378 AC XY: 2599 AN XY: 688020

Gnomad4 AFR exome AF: 0.0384

Gnomad4 AMR exome AF: 0.00218

Gnomad4 ASJ exome AF: 0.00102

Gnomad4 EAS exome AF: 0.000907

Gnomad4 SAS exome AF: 0.00114

Gnomad4 FIN exome AF: 0.00151

Gnomad4 NFE exome AF: 0.00377

Gnomad4 OTH exome AF: 0.00512

GnomAD4 genome AF: 0.00993 AC: 1479 AN: 148974 Hom.: 18 Cov.: 32 AF XY: 0.00984 AC XY: 714 AN XY: 72562

Gnomad4 AFR AF: 0.0333

Gnomad4 AMR AF: 0.00300

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000406

Gnomad4 NFE AF: 0.000924

Gnomad4 OTH AF: 0.00681

Bravo AF: 0.0113

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Sep 07, 2017

- -

Generalized epilepsy-paroxysmal dyskinesia syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

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: rs112408409; hg19: chr10-78704741;