dbSNP rs6786049: KCNMB3:c.*1548G>A (chr3-179241356-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000485523.5(KCNMB3):c.*1548G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0797 in 154,220 control chromosomes in the GnomAD database, including 526 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 0.079 ( 506 hom., cov: 32)

Exomes 𝑓: 0.11 ( 20 hom. )

Consequence

KCNMB3
ENST00000485523.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.130

Publications

4 publications found

Variant links:

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]

KCNMB3 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0999 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMB3	NM_001163677.2 link	c.454-1292G>A		intron_variant	Intron 3 of 3		NP_001157149.1	Q9NPA1-5
KCNMB3	NR_028135.2 link	n.1812-1292G>A		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
KCNMB3	ENST00000485523.5 link	c.*1548G>A	3_prime_UTR_variant	Exon 4 of 4	1	ENSP00000418536.1	Q9NPA1-4
KCNMB3	ENST00000392686.6 link	n.*96-1292G>A	intron_variant	Intron 4 of 4	1	ENSP00000376452.2	Q9NPA1-4
KCNMB3	ENST00000497599.5 link	c.454-1292G>A	intron_variant	Intron 3 of 3	2	ENSP00000417091.1	Q9NPA1-5
KCNMB3	ENST00000486944.2 link	c.153-1292G>A	intron_variant	Intron 1 of 1	3	ENSP00000479162.1	A0A087WV41

Frequencies

GnomAD3 genomes

AF:

0.0791

AC:

12027

AN:

151980

Hom.:

506

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.128

Gnomad AMR

AF:

0.0910

Gnomad ASJ

AF:

0.0464

Gnomad EAS

AF:

0.0981

Gnomad SAS

AF:

0.0811

Gnomad FIN

AF:

0.0682

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0637

Gnomad OTH

AF:

0.0692

GnomAD4 exome

AF:

0.115

AC:

243

AN:

2122

Hom.:

Cov.:

AF XY:

0.120

AC XY:

127

AN XY:

1062

show subpopulations

African (AFR)

AF:

0.176

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.0543

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.121

AC:

192

AN:

1582

European-Non Finnish (NFE)

AF:

0.0920

AC:

AN:

174

Other (OTH)

AF:

0.0904

AC:

AN:

188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.0792

AC:

12047

AN:

152098

Hom.:

506

Cov.:

AF XY:

0.0803

AC XY:

5971

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.103

AC:

4252

AN:

41482

American (AMR)

AF:

0.0920

AC:

1405

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0464

AC:

161

AN:

3468

East Asian (EAS)

AF:

0.0980

AC:

507

AN:

5174

South Asian (SAS)

AF:

0.0809

AC:

390

AN:

4820

European-Finnish (FIN)

AF:

0.0682

AC:

721

AN:

10574

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0636

AC:

4325

AN:

67978

Other (OTH)

AF:

0.0685

AC:

145

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

555

1110

1665

2220

2775

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

276

414

552

690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0745

Hom.:

Bravo

AF:

0.0834

Asia WGS

AF:

0.0790

AC:

274

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.8

(source)

DANN

Benign

0.68

PhyloP100

0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over