20-49372988-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_004975.4(KCNB1):c.2572A>G(p.Ile858Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000756 in 1,455,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

KCNB1
NM_004975.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.02

Publications

0 publications found

Variant links:

Genes affected

KCNB1 (HGNC:6231): (potassium voltage-gated channel subfamily B member 1) 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 and its activity is modulated by some other family members. [provided by RefSeq, Jul 2008]

KCNB1 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
developmental and epileptic encephalopathy, 26
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KCNB1 links:

ENSG00000290421 (HGNC:):

ENSG00000290421 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17979088).

BP6

Variant 20-49372988-T-C is Benign according to our data. Variant chr20-49372988-T-C is described in ClinVar as [Benign]. Clinvar id is 2160995.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNB1	NM_004975.4 link	c.2572A>G	p.Ile858Val	missense_variant	Exon 2 of 2	ENST00000371741.6	NP_004966.1	Q14721
KCNB1	XM_011528799.3 link	c.2572A>G	p.Ile858Val	missense_variant	Exon 3 of 3		XP_011527101.1	Q14721
LOC105372649	XR_001754659.2 link	n.1201+40964T>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNB1	ENST00000371741.6 link	c.2572A>G	p.Ile858Val	missense_variant	Exon 2 of 2	1	NM_004975.4	ENSP00000360806.3		Q14721

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000245

AC:

AN:

244786

AF XY:

0.0000227

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000543

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000756

AC:

AN:

1455348

Hom.:

Cov.:

AF XY:

0.00000691

AC XY:

AN XY:

723952

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33188

American (AMR)

AF:

0.00

AC:

AN:

43866

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25688

East Asian (EAS)

AF:

0.00

AC:

AN:

39664

South Asian (SAS)

AF:

0.00

AC:

AN:

85288

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53186

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5196

European-Non Finnish (NFE)

AF:

0.00000902

AC:

AN:

1109250

Other (OTH)

AF:

0.0000167

AC:

AN:

60022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 26

Benign:1

Sep 06, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Uncertain

0.013

BayesDel_noAF

Benign

-0.090

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.28

T;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.24

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.71

.;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.18

T;T

MetaSVM

Uncertain

0.58

MutationAssessor

Benign

0.97

L;L

PhyloP100

4.0

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.090

N;.

REVEL

Uncertain

0.34

Sift

Uncertain

0.0090

D;.

Sift4G

Uncertain

0.048

D;D

Polyphen

0.20

B;B

Vest4

0.39

MutPred

0.31

Loss of glycosylation at S857 (P = 0.1703);Loss of glycosylation at S857 (P = 0.1703);

MVP

0.43

MPC

0.16

ClinPred

0.10

GERP RS

3.9

Varity_R

0.063

gMVP

0.35

Mutation Taster

=89/11

polymorphism

(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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20-49372988-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over