Variant 3-178842793-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_181361.3(KCNMB2):c.564A>C(p.Thr188=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,613,076 control chromosomes in the GnomAD database, including 276,724 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.64 ( 33474 hom., cov: 32)

Exomes 𝑓: 0.57 ( 243250 hom. )

Consequence

KCNMB2
NM_181361.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.798

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:

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

KCNMB2-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 3-178842793-A-C is Benign according to our data. Variant chr3-178842793-A-C is described in ClinVar as [Benign]. Clinvar id is 1273272.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.798 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNMB2	NM_181361.3 linkuse as main transcript	c.564A>C	p.Thr188=	synonymous_variant	5/5	ENST00000452583.6
KCNMB2-AS1	NR_126560.1 linkuse as main transcript	n.247+16696T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNMB2	ENST00000452583.6 linkuse as main transcript	c.564A>C	p.Thr188=	synonymous_variant	5/5	1	NM_181361.3	P1
KCNMB2-AS1	ENST00000437488.5 linkuse as main transcript	n.194+16696T>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.644

AC:

97853

AN:

151868

Hom.:

33430

Cov.:

show subpopulations

Gnomad AFR

AF:

0.873

Gnomad AMI

AF:

0.586

Gnomad AMR

AF:

0.555

Gnomad ASJ

AF:

0.617

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.523

Gnomad FIN

AF:

0.538

Gnomad MID

AF:

0.692

Gnomad NFE

AF:

0.584

Gnomad OTH

AF:

0.631

GnomAD3 exomes

AF:

0.552

AC:

138390

AN:

250876

Hom.:

40353

AF XY:

0.551

AC XY:

74704

AN XY:

135586

show subpopulations

Gnomad AFR exome

AF:

0.878

Gnomad AMR exome

AF:

0.478

Gnomad ASJ exome

AF:

0.607

Gnomad EAS exome

AF:

0.228

Gnomad SAS exome

AF:

0.523

Gnomad FIN exome

AF:

0.549

Gnomad NFE exome

AF:

0.582

Gnomad OTH exome

AF:

0.581

GnomAD4 exome

AF:

0.571

AC:

834812

AN:

1461088

Hom.:

243250

Cov.:

AF XY:

0.571

AC XY:

414718

AN XY:

726868

show subpopulations

Gnomad4 AFR exome

AF:

0.887

Gnomad4 AMR exome

AF:

0.489

Gnomad4 ASJ exome

AF:

0.610

Gnomad4 EAS exome

AF:

0.277

Gnomad4 SAS exome

AF:

0.526

Gnomad4 FIN exome

AF:

0.546

Gnomad4 NFE exome

AF:

0.579

Gnomad4 OTH exome

AF:

0.582

GnomAD4 genome

AF:

0.644

AC:

97952

AN:

151988

Hom.:

33474

Cov.:

AF XY:

0.637

AC XY:

47339

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.873

Gnomad4 AMR

AF:

0.556

Gnomad4 ASJ

AF:

0.617

Gnomad4 EAS

AF:

0.239

Gnomad4 SAS

AF:

0.522

Gnomad4 FIN

AF:

0.538

Gnomad4 NFE

AF:

0.583

Gnomad4 OTH

AF:

0.625

Alfa

AF:

0.614

Hom.:

20770

Bravo

AF:

0.653

Asia WGS

AF:

0.444

AC:

1546

AN:

3478

EpiCase

AF:

0.597

EpiControl

AF:

0.585

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 09, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

Cadd

Benign

6.9

Dann

Benign

0.74

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over