dbSNP rs3787318: KCNB1:c.567+40384A>G (chr20-49441530-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004975.4(KCNB1):c.567+40384A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0323 in 152,200 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.032 ( 91 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCNB1
NM_004975.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.862

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNB1	NM_004975.4 link	c.567+40384A>G		intron_variant	Intron 1 of 1	ENST00000371741.6	NP_004966.1	Q14721
KCNB1	XM_011528799.3 link	c.567+40384A>G		intron_variant	Intron 2 of 2		XP_011527101.1	Q14721

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNB1	ENST00000371741.6 link	c.567+40384A>G	intron_variant	Intron 1 of 1	1	NM_004975.4	ENSP00000360806.3	Q14721
KCNB1	ENST00000635465.1 link	c.567+40384A>G	intron_variant	Intron 2 of 2	1		ENSP00000489193.1	Q14721
ENSG00000290421	ENST00000637341.1 link	n.1564T>C	non_coding_transcript_exon_variant	Exon 8 of 8	5
KCNB1	ENST00000635878.1 link	c.96+40384A>G	intron_variant	Intron 1 of 2	5		ENSP00000489908.1	A0A1B0GU02

Frequencies

GnomAD3 genomes

AF:

0.0323

AC:

4911

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00826

Gnomad AMI

AF:

0.0965

Gnomad AMR

AF:

0.0335

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.0826

Gnomad SAS

AF:

0.0593

Gnomad FIN

AF:

0.0199

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0428

Gnomad OTH

AF:

0.0353

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.0323

AC:

4911

AN:

152200

Hom.:

Cov.:

AF XY:

0.0321

AC XY:

2391

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.00826

AC:

343

AN:

41542

American (AMR)

AF:

0.0334

AC:

510

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0176

AC:

AN:

3468

East Asian (EAS)

AF:

0.0828

AC:

427

AN:

5160

South Asian (SAS)

AF:

0.0592

AC:

285

AN:

4816

European-Finnish (FIN)

AF:

0.0199

AC:

211

AN:

10604

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0428

AC:

2909

AN:

68000

Other (OTH)

AF:

0.0350

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

239

478

716

955

1194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0378

Hom.:

Bravo

AF:

0.0321

Asia WGS

AF:

0.0670

AC:

235

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.68

(source)

DANN

Benign

0.51

PhyloP100

-0.86

Mutation Taster

=100/0

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over