Variant 8-72567905-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004770.3(KCNB2):c.171C>G(p.Pro57Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 1,613,918 control chromosomes in the GnomAD database, including 981 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 143 hom., cov: 32)

Exomes 𝑓: 0.026 ( 838 hom. )

Consequence

KCNB2
NM_004770.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.172

Variant links:

Genes affected

KCNB2 (HGNC:6232): (potassium voltage-gated channel subfamily B member 2) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shab-related subfamily. This member is a delayed rectifier potassium channel. The gene is expressed in gastrointestinal smooth muscle cells. [provided by RefSeq, Jul 2008]

KCNB2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 8-72567905-C-G is Benign according to our data. Variant chr8-72567905-C-G is described in ClinVar as [Benign]. Clinvar id is 1282555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.172 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNB2	NM_004770.3 linkuse as main transcript	c.171C>G	p.Pro57Pro	synonymous_variant	2/3	ENST00000523207.2	NP_004761.2	Q92953

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNB2	ENST00000523207.2 linkuse as main transcript	c.171C>G	p.Pro57Pro	synonymous_variant	2/3	1	NM_004770.3	ENSP00000430846.1		Q92953

Frequencies

GnomAD3 genomes

AF:

0.0357

AC:

5425

AN:

152076

Hom.:

144

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0625

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0283

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0922

Gnomad FIN

AF:

0.0270

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0217

Gnomad OTH

AF:

0.0368

GnomAD3 exomes

AF:

0.0358

AC:

8990

AN:

250796

Hom.:

274

AF XY:

0.0373

AC XY:

5052

AN XY:

135602

show subpopulations

Gnomad AFR exome

AF:

0.0630

Gnomad AMR exome

AF:

0.0495

Gnomad ASJ exome

AF:

0.0340

Gnomad EAS exome

AF:

0.000490

Gnomad SAS exome

AF:

0.0867

Gnomad FIN exome

AF:

0.0274

Gnomad NFE exome

AF:

0.0220

Gnomad OTH exome

AF:

0.0281

GnomAD4 exome

AF:

0.0263

AC:

38438

AN:

1461724

Hom.:

838

Cov.:

AF XY:

0.0281

AC XY:

20441

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.0643

Gnomad4 AMR exome

AF:

0.0480

Gnomad4 ASJ exome

AF:

0.0311

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.0873

Gnomad4 FIN exome

AF:

0.0263

Gnomad4 NFE exome

AF:

0.0203

Gnomad4 OTH exome

AF:

0.0260

GnomAD4 genome

AF:

0.0357

AC:

5430

AN:

152194

Hom.:

143

Cov.:

AF XY:

0.0367

AC XY:

2728

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0624

Gnomad4 AMR

AF:

0.0285

Gnomad4 ASJ

AF:

0.0285

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0923

Gnomad4 FIN

AF:

0.0270

Gnomad4 NFE

AF:

0.0217

Gnomad4 OTH

AF:

0.0360

Alfa

AF:

0.0191

Hom.:

Bravo

AF:

0.0350

Asia WGS

AF:

0.0350

AC:

121

AN:

3478

EpiCase

AF:

0.0204

EpiControl

AF:

0.0248

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 01, 2020	- -

KCNB2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 27, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

6.6

DANN

Benign

0.73

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