chr3-178304602-A-G

Variant names:

• chr3-178304602-A-G
• rs6791314
• ENST00000437510.5:c.-68+31596A>G

Variant summary

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

The ENST00000437510.5(KCNMB2):​c.-68+31596A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 152,046 control chromosomes in the GnomAD database, including 32,839 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 0.65 (32839 hom., cov: 32)
• Consequence: KCNMB2 ENST00000437510.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.692
• Publications: 3 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]

ENSG00000223930 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 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
	LOC105374235	NR_188690.1		n.210-4909T>C		intron	N/A
	LOC105374235	NR_188692.1		n.156+67149T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB2	ENST00000437510.5	TSL:4	c.-68+31596A>G		intron	N/A	ENSP00000395807.1
	ENSG00000223930	ENST00000414475.1	TSL:5	n.103+80605T>C		intron	N/A
	ENSG00000223930	ENST00000439810.6	TSL:4	n.281-26545T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99198 AN: 151928 Hom.: 32807 Cov.: 32

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.678

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

GnomAD4 genome AF: 0.653 AC: 99275 AN: 152046 Hom.: 32839 Cov.: 32 AF XY: 0.651 AC XY: 48422 AN XY: 74332

African (AFR) AF: 0.770 AC: 31957 AN: 41494

American (AMR) AF: 0.631 AC: 9647 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2584 AN: 3472

East Asian (EAS) AF: 0.417 AC: 2152 AN: 5160

South Asian (SAS) AF: 0.599 AC: 2892 AN: 4832

European-Finnish (FIN) AF: 0.625 AC: 6597 AN: 10562

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.607 AC: 41258 AN: 67924

Other (OTH) AF: 0.671 AC: 1418 AN: 2112

Alfa AF: 0.615 Hom.: 122291

Bravo AF: 0.656

Asia WGS AF: 0.475 AC: 1645 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.17
DANN	Benign	0.36
PhyloP100		-0.69

Splicing

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

Other links and lift over

dbSNP: rs6791314; hg19: chr3-178022390;