Genetic Variant NM_014505.6:c.314A>G (chr12-70367048-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014505.6(KCNMB4):c.314A>G(p.His105Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000502 in 1,395,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

KCNMB4
NM_014505.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.56

Publications

0 publications found

Variant links:

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]

KCNMB4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.088033944).

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.314A>G	p.His105Arg	missense	Exon 1 of 3	NP_055320.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMB4	ENST00000258111.5	TSL:1 MANE Select	c.314A>G	p.His105Arg	missense	Exon 1 of 3	ENSP00000258111.4	Q86W47

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000938

AC:

AN:

213202

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000203

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000502

AC:

AN:

1395018

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

686332

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32380

American (AMR)

AF:

0.00

AC:

AN:

40652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23936

East Asian (EAS)

AF:

0.00

AC:

AN:

37642

South Asian (SAS)

AF:

0.00

AC:

AN:

79196

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5532

European-Non Finnish (NFE)

AF:

0.00000653

AC:

AN:

1072676

Other (OTH)

AF:

0.00

AC:

AN:

57512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.076

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.72

M_CAP

Benign

0.0078

MetaRNN

Benign

0.088

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.060

PhyloP100

3.6

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.67

REVEL

Benign

0.095

Sift

Benign

0.12

Sift4G

Benign

0.85

Polyphen

0.0

Vest4

0.099

MutPred

0.50

Gain of phosphorylation at S102 (P = 0.1063)

MVP

0.068

MPC

1.3

ClinPred

0.13

GERP RS

2.2

Varity_R

0.23

gMVP

0.75

Mutation Taster

=67/33

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over