rs115965187

Variant names:

• chr3-179265272-C-T
• rs115965187
• NM_171828.3:c.62+1377G>A

Variant summary

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

The NM_171828.3(KCNMB3):​c.62+1377G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 152,294 control chromosomes in the GnomAD database, including 73 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 0.015 (73 hom., cov: 32)
• Consequence: KCNMB3 NM_171828.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186
• Publications: 2 publications found

Genes affected

KCNMB3 (HGNC:6287): (potassium calcium-activated channel subfamily M regulatory beta subunit 3) 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 may partially inactivate or slightly decrease the activation time of MaxiK alpha subunit currents. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 22. [provided by RefSeq, Jul 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0508 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_171828.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB3	NM_171828.3		c.62+1377G>A		intron	N/A	NP_741979.1	Q9NPA1-2
	KCNMB3	NM_001163677.2		c.62+1377G>A		intron	N/A	NP_001157149.1	Q9NPA1-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB3	ENST00000349697.2	TSL:5	c.62+1377G>A		intron	N/A	ENSP00000327866.2	Q9NPA1-2
	KCNMB3	ENST00000497599.5	TSL:2	c.62+1377G>A		intron	N/A	ENSP00000417091.1	Q9NPA1-5

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2347 AN: 152176 Hom.: 72 Cov.: 32

Gnomad AFR AF: 0.0528

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00746

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0134

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

GnomAD4 genome AF: 0.0154 AC: 2348 AN: 152294 Hom.: 73 Cov.: 32 AF XY: 0.0149 AC XY: 1112 AN XY: 74478

African (AFR) AF: 0.0527 AC: 2188 AN: 41530

American (AMR) AF: 0.00745 AC: 114 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68030

Other (OTH) AF: 0.0132 AC: 28 AN: 2116

Alfa AF: 0.0106 Hom.: 9

Bravo AF: 0.0172

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.2
DANN	Benign	0.47
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs115965187; hg19: chr3-178983060;