dbSNP rs9637454: KCNMB2:c.-68+3063G>A (chr3-178539774-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_181361.3(KCNMB2):c.-68+3063G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 151,990 control chromosomes in the GnomAD database, including 4,873 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 0.23 ( 4873 hom., cov: 32)

Consequence

KCNMB2
NM_181361.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.823

Publications

17 publications found

Variant links:

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]

KCNMB2 links:

ENSG00000275163 (HGNC:):

ENSG00000275163 links:

KCNMB2-AS1 (HGNC:51409): (KCNMB2 antisense RNA 1)

KCNMB2-AS1 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 (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KCNMB2	NM_181361.3 link	c.-68+3063G>A	intron_variant	Intron 1 of 4	ENST00000452583.6	NP_852006.1	Q9Y691B5BNW5
KCNMB2-AS1	NR_126560.1 link	n.575-2378C>T	intron_variant	Intron 5 of 7
KCNMB2-AS1	NR_126561.1 link	n.638-13149C>T	intron_variant	Intron 5 of 5
KCNMB2	XM_011512325.3 link	c.-145+3063G>A	intron_variant	Intron 1 of 5		XP_011510627.1	Q9Y691

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMB2	ENST00000452583.6 link	c.-68+3063G>A		intron_variant	Intron 1 of 4	1	NM_181361.3	ENSP00000397483.1		Q9Y691
ENSG00000275163	ENST00000614557.1 link	c.-68+120399G>A		intron_variant	Intron 1 of 4	2		ENSP00000483415.1

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35485

AN:

151872

Hom.:

4869

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0860

Gnomad AMI

AF:

0.256

Gnomad AMR

AF:

0.274

Gnomad ASJ

AF:

0.332

Gnomad EAS

AF:

0.433

Gnomad SAS

AF:

0.292

Gnomad FIN

AF:

0.350

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.249

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

GnomAD4 genome

AF:

0.234

AC:

35495

AN:

151990

Hom.:

4873

Cov.:

AF XY:

0.240

AC XY:

17794

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.0858

AC:

3559

AN:

41480

American (AMR)

AF:

0.274

AC:

4176

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

1151

AN:

3468

East Asian (EAS)

AF:

0.433

AC:

2234

AN:

5158

South Asian (SAS)

AF:

0.293

AC:

1408

AN:

4810

European-Finnish (FIN)

AF:

0.350

AC:

3691

AN:

10556

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.271

AC:

18440

AN:

67946

Other (OTH)

AF:

0.256

AC:

540

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1329

2658

3987

5316

6645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

388

776

1164

1552

1940

<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:

0.247

Hom.:

615

Bravo

AF:

0.222

Asia WGS

AF:

0.354

AC:

1237

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.50

(source)

DANN

Benign

0.65

PhyloP100

-0.82

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over