chr3-178403079-A-C

Position:

• chr3-178403079-A-C

Variant summary

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

The ENST00000437510.5(KCNMB2):​c.-68+130073A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,056 control chromosomes in the GnomAD database, including 1,457 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 0.12 (1457 hom., cov: 32)
• Consequence: KCNMB2 ENST00000437510.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192

Genes affected

KCNMB2 (HGNC:6286): (potassium calcium-activated channel subfamily M regulatory beta subunit 2) MaxiK channels are large conductance, voltage and calcium-sensitive potassium channels which are fundamental to the control of smooth muscle tone and neuronal excitability. MaxiK channels can be formed by 2 subunits: the pore-forming alpha subunit and the modulatory beta subunit. The protein encoded by this gene is an auxiliary beta subunit which decreases the activation time of MaxiK alpha subunit currents. Alternative splicing results in multiple transcript variants of this gene. Additional variants are discussed in the literature, but their full length nature has not been described. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNMB2	ENST00000437510.5	c.-68+130073A>C		intron_variant		4		ENSP00000395807

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17690 AN: 151940 Hom.: 1458 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0821

Gnomad ASJ AF: 0.0757

Gnomad EAS AF: 0.0873

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0664

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.116 AC: 17704 AN: 152056 Hom.: 1457 Cov.: 32 AF XY: 0.115 AC XY: 8535 AN XY: 74328

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.0819

Gnomad4 ASJ AF: 0.0757

Gnomad4 EAS AF: 0.0873

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.0649

Gnomad4 NFE AF: 0.0664

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0536 Hom.: 94

Bravo AF: 0.121

Asia WGS AF: 0.127 AC: 439 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9846680; hg19: chr3-178120867;