chr3-178403079-A-C

Variant names:

• chr3-178403079-A-C
• rs9846680
• ENST00000437510.5:c.-68+130073A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000437510.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB2	ENST00000437510.5	TSL:4	c.-68+130073A>C		intron	N/A	ENSP00000395807.1

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

African (AFR) AF: 0.229 AC: 9476 AN: 41452

American (AMR) AF: 0.0819 AC: 1251 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0757 AC: 263 AN: 3472

East Asian (EAS) AF: 0.0873 AC: 451 AN: 5164

South Asian (SAS) AF: 0.147 AC: 707 AN: 4808

European-Finnish (FIN) AF: 0.0649 AC: 688 AN: 10598

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0664 AC: 4512 AN: 67974

Other (OTH) AF: 0.111 AC: 234 AN: 2106

Alfa AF: 0.0651 Hom.: 199

Bravo AF: 0.121

Asia WGS AF: 0.127 AC: 439 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.70
PhyloP100		0.19

Splicing

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

Other links and lift over

dbSNP: rs9846680; hg19: chr3-178120867;