chr20-49373454-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_004975.4(KCNB1):c.2106G>A(p.Ala702Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000491 in 1,614,088 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 2 hom. )

Consequence

KCNB1
NM_004975.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.73

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 links:

ENSG00000290421 (HGNC:):

ENSG00000290421 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 20-49373454-C-T is Benign according to our data. Variant chr20-49373454-C-T is described in ClinVar as [Benign]. Clinvar id is 382943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.73 with no splicing effect.

BS2

High AC in GnomAd4 at 335 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNB1	NM_004975.4 link	c.2106G>A	p.Ala702Ala	synonymous_variant	Exon 2 of 2	ENST00000371741.6	NP_004966.1	Q14721
KCNB1	XM_011528799.3 link	c.2106G>A	p.Ala702Ala	synonymous_variant	Exon 3 of 3		XP_011527101.1	Q14721
LOC105372649	XR_001754659.2 link	n.1201+41430C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNB1	ENST00000371741.6 link	c.2106G>A	p.Ala702Ala	synonymous_variant	Exon 2 of 2	1	NM_004975.4	ENSP00000360806.3	Q14721
KCNB1	ENST00000635465.1 link	c.2106G>A	p.Ala702Ala	synonymous_variant	Exon 3 of 3	1		ENSP00000489193.1	Q14721
KCNB1	ENST00000635878.1 link	c.97-74071G>A		intron_variant	Intron 1 of 2	5		ENSP00000489908.1	A0A1B0GU02
ENSG00000290421	ENST00000637341.1 link	n.206+41430C>T		intron_variant	Intron 2 of 7	5

Frequencies

GnomAD3 genomes

AF:

0.00219

AC:

333

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00727

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.000658

AC:

165

AN:

250862

Hom.:

AF XY:

0.000487

AC XY:

AN XY:

135630

show subpopulations

Gnomad AFR exome

AF:

0.00735

Gnomad AMR exome

AF:

0.000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000490

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000883

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000313

AC:

458

AN:

1461872

Hom.:

Cov.:

AF XY:

0.000267

AC XY:

194

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00899

Gnomad4 AMR exome

AF:

0.000492

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000756

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000342

Gnomad4 OTH exome

AF:

0.000513

GnomAD4 genome

AF:

0.00220

AC:

335

AN:

152216

Hom.:

Cov.:

AF XY:

0.00210

AC XY:

156

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00730

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00131

Hom.:

Bravo

AF:

0.00232

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KCNB1: BP4, BP7, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Developmental and epileptic encephalopathy, 26

Benign:1

Jan 19, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Aug 17, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.59

DANN

Benign

0.61

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