Variant chr8-72937968-G-A 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.2613G>A(p.Val871=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,613,696 control chromosomes in the GnomAD database, including 127,773 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9479 hom., cov: 32)

Exomes 𝑓: 0.39 ( 118294 hom. )

Consequence

KCNB2
NM_004770.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.13

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=-0.8).

BP6

Variant 8-72937968-G-A is Benign according to our data. Variant chr8-72937968-G-A is described in ClinVar as [Benign]. Clinvar id is 1226816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 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.2613G>A	p.Val871=	synonymous_variant	3/3	ENST00000523207.2	NP_004761.2
KCNB2	XM_017013982.2 linkuse as main transcript	c.1878G>A	p.Val626=	synonymous_variant	2/2		XP_016869471.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNB2	ENST00000523207.2 linkuse as main transcript	c.2613G>A	p.Val871=	synonymous_variant	3/3	1	NM_004770.3	ENSP00000430846	P1

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

51334

AN:

151840

Hom.:

9480

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.488

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.368

Gnomad EAS

AF:

0.0967

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.421

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.346

GnomAD3 exomes

AF:

0.334

AC:

83988

AN:

251170

Hom.:

15420

AF XY:

0.338

AC XY:

45876

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.255

Gnomad ASJ exome

AF:

0.361

Gnomad EAS exome

AF:

0.0991

Gnomad SAS exome

AF:

0.264

Gnomad FIN exome

AF:

0.408

Gnomad NFE exome

AF:

0.415

Gnomad OTH exome

AF:

0.348

GnomAD4 exome

AF:

0.394

AC:

576587

AN:

1461736

Hom.:

118294

Cov.:

AF XY:

0.391

AC XY:

284449

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.225

Gnomad4 AMR exome

AF:

0.259

Gnomad4 ASJ exome

AF:

0.361

Gnomad4 EAS exome

AF:

0.0932

Gnomad4 SAS exome

AF:

0.265

Gnomad4 FIN exome

AF:

0.406

Gnomad4 NFE exome

AF:

0.428

Gnomad4 OTH exome

AF:

0.371

GnomAD4 genome

AF:

0.338

AC:

51350

AN:

151960

Hom.:

9479

Cov.:

AF XY:

0.335

AC XY:

24890

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.226

Gnomad4 AMR

AF:

0.309

Gnomad4 ASJ

AF:

0.368

Gnomad4 EAS

AF:

0.0967

Gnomad4 SAS

AF:

0.251

Gnomad4 FIN

AF:

0.421

Gnomad4 NFE

AF:

0.421

Gnomad4 OTH

AF:

0.345

Alfa

AF:

0.400

Hom.:

23130

Bravo

AF:

0.325

Asia WGS

AF:

0.229

AC:

795

AN:

3478

EpiCase

AF:

0.416

EpiControl

AF:

0.416

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	Feb 28, 2019	- -

KCNB2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 16, 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

-0.80

CADD

Benign

2.1

DANN

Benign

0.59

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