Genetic Variant KCNB2:c.579+174914C>T (chr8-72743227-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_004770.3(KCNB2):c.579+174914C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,174 control chromosomes in the GnomAD database, including 41,148 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 ( 41148 hom., cov: 33)

Consequence

KCNB2
NM_004770.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.327

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

KCNB2 links:

ENSG00000253726 (HGNC:):

ENSG00000253726 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=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNB2	NM_004770.3 link	c.579+174914C>T		intron_variant	Intron 2 of 2	ENST00000523207.2	NP_004761.2	Q92953
LOC101926908	NR_110656.1 link	n.58-6111C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNB2	ENST00000523207.2 link	c.579+174914C>T		intron_variant	Intron 2 of 2	1	NM_004770.3	ENSP00000430846.1		Q92953
ENSG00000253726	ENST00000519427.1 link	n.58-6111C>T		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.724

AC:

110040

AN:

152054

Hom.:

41085

Cov.:

show subpopulations

Gnomad AFR

AF:

0.906

Gnomad AMI

AF:

0.670

Gnomad AMR

AF:

0.617

Gnomad ASJ

AF:

0.595

Gnomad EAS

AF:

0.434

Gnomad SAS

AF:

0.574

Gnomad FIN

AF:

0.632

Gnomad MID

AF:

0.649

Gnomad NFE

AF:

0.692

Gnomad OTH

AF:

0.699

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.724

AC:

110169

AN:

152174

Hom.:

41148

Cov.:

AF XY:

0.715

AC XY:

53197

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.906

AC:

37629

AN:

41542

American (AMR)

AF:

0.617

AC:

9433

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.595

AC:

2064

AN:

3470

East Asian (EAS)

AF:

0.435

AC:

2250

AN:

5172

South Asian (SAS)

AF:

0.575

AC:

2769

AN:

4816

European-Finnish (FIN)

AF:

0.632

AC:

6678

AN:

10564

Middle Eastern (MID)

AF:

0.639

AC:

188

AN:

294

European-Non Finnish (NFE)

AF:

0.692

AC:

47065

AN:

68004

Other (OTH)

AF:

0.701

AC:

1482

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1493

2986

4480

5973

7466

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

828

1656

2484

3312

4140

<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:

0.703

Hom.:

6396

Bravo

AF:

0.733

Asia WGS

AF:

0.556

AC:

1939

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.0

(source)

DANN

Benign

0.75

PhyloP100

-0.33

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

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