12-70423499-A-G

Variant names:

• chr12-70423499-A-G
• rs787931
• NM_014505.6:c.465-6986A>G

Variant summary

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

The NM_014505.6(KCNMB4):​c.465-6986A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 151,566 control chromosomes in the GnomAD database, including 2,597 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 0.17 (2597 hom., cov: 31)
• Consequence: KCNMB4 NM_014505.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.566
• Publications: 4 publications found

Genes affected

KCNMB4 (HGNC:6289): (potassium calcium-activated channel subfamily M regulatory beta subunit 4) 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 slows activation kinetics, leads to steeper calcium sensitivity, and shifts the voltage range of current activation to more negative potentials than does the beta 1 subunit. [provided by RefSeq, Jul 2008]

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 (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014505.6. 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
	KCNMB4	NM_014505.6	MANE Select	c.465-6986A>G		intron	N/A	NP_055320.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB4	ENST00000258111.5	TSL:1 MANE Select	c.465-6986A>G		intron	N/A	ENSP00000258111.4	Q86W47
	KCNMB4	ENST00000531884.1	TSL:2	n.*136+650A>G		intron	N/A	ENSP00000431137.1	H0YC85

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25871 AN: 151450 Hom.: 2584 Cov.: 31

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.171 AC: 25900 AN: 151566 Hom.: 2597 Cov.: 31 AF XY: 0.175 AC XY: 12948 AN XY: 74040

African (AFR) AF: 0.237 AC: 9793 AN: 41256

American (AMR) AF: 0.207 AC: 3144 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 373 AN: 3464

East Asian (EAS) AF: 0.341 AC: 1757 AN: 5150

South Asian (SAS) AF: 0.254 AC: 1215 AN: 4784

European-Finnish (FIN) AF: 0.159 AC: 1668 AN: 10492

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7545 AN: 67886

Other (OTH) AF: 0.159 AC: 336 AN: 2108

Alfa AF: 0.125 Hom.: 1955

Bravo AF: 0.178

Asia WGS AF: 0.336 AC: 1168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.29
PhyloP100		0.57
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs787931; hg19: chr12-70817279;