dbSNP rs237477: KCNB1:c.567+41003G>A (chr20-49440911-C-T) – 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+41003G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 152,196 control chromosomes in the GnomAD database, including 40,419 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 0.72 ( 40395 hom., cov: 32)

Exomes 𝑓: 0.71 ( 24 hom. )

Consequence

KCNB1
NM_004975.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.151

Publications

4 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KCNB1 links:

ENSG00000290421 (HGNC:):

ENSG00000290421 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_004975.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004975.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNB1	NM_004975.4	MANE Select	c.567+41003G>A		intron	N/A	NP_004966.1	Q14721

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCNB1	ENST00000371741.6	TSL:1 MANE Select	c.567+41003G>A	intron	N/A	ENSP00000360806.3	Q14721
KCNB1	ENST00000635465.1	TSL:1	c.567+41003G>A	intron	N/A	ENSP00000489193.1	Q14721
KCNB1	ENST00000635878.1	TSL:5	c.96+41003G>A	intron	N/A	ENSP00000489908.1	A0A1B0GU02

Frequencies

GnomAD3 genomes

AF:

0.715

AC:

108658

AN:

151982

Hom.:

40342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.930

Gnomad AMI

AF:

0.508

Gnomad AMR

AF:

0.708

Gnomad ASJ

AF:

0.720

Gnomad EAS

AF:

0.708

Gnomad SAS

AF:

0.717

Gnomad FIN

AF:

0.556

Gnomad MID

AF:

0.783

Gnomad NFE

AF:

0.612

Gnomad OTH

AF:

0.726

GnomAD4 exome

AF:

0.713

AC:

AN:

Hom.:

Cov.:

AF XY:

0.722

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.718

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.715

AC:

108764

AN:

152102

Hom.:

40395

Cov.:

AF XY:

0.714

AC XY:

53081

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.930

AC:

38615

AN:

41528

American (AMR)

AF:

0.708

AC:

10832

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.720

AC:

2497

AN:

3468

East Asian (EAS)

AF:

0.709

AC:

3668

AN:

5176

South Asian (SAS)

AF:

0.718

AC:

3454

AN:

4812

European-Finnish (FIN)

AF:

0.556

AC:

5865

AN:

10550

Middle Eastern (MID)

AF:

0.789

AC:

232

AN:

294

European-Non Finnish (NFE)

AF:

0.612

AC:

41618

AN:

67952

Other (OTH)

AF:

0.719

AC:

1521

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1460

2920

4380

5840

7300

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

820

1640

2460

3280

4100

<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:

0.651

Hom.:

64093

Bravo

AF:

0.734

Asia WGS

AF:

0.709

AC:

2466

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.7

(source)

DANN

Benign

0.41

PhyloP100

-0.15

Mutation Taster

=100/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over