rs237476

Variant names:

• chr20-49434845-G-T
• rs237476
• NM_004975.4:c.567+47069C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004975.4(KCNB1):​c.567+47069C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 151,884 control chromosomes in the GnomAD database, including 21,867 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 0.53 (21867 hom., cov: 31)
• Consequence: KCNB1 NM_004975.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 5 publications found

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

ENSG00000290421 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNB1	NM_004975.4	c.567+47069C>A		intron_variant	Intron 1 of 1	ENST00000371741.6	NP_004966.1
KCNB1	XM_011528799.3	c.567+47069C>A		intron_variant	Intron 2 of 2		XP_011527101.1
LOC105372649	XR_001754659.2	n.1318-3743G>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNB1	ENST00000371741.6	c.567+47069C>A		intron_variant	Intron 1 of 1	1	NM_004975.4	ENSP00000360806.3

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80512 AN: 151766 Hom.: 21843 Cov.: 31

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.531 AC: 80585 AN: 151884 Hom.: 21867 Cov.: 31 AF XY: 0.530 AC XY: 39367 AN XY: 74242

African (AFR) AF: 0.651 AC: 26960 AN: 41390

American (AMR) AF: 0.595 AC: 9092 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1924 AN: 3470

East Asian (EAS) AF: 0.493 AC: 2541 AN: 5154

South Asian (SAS) AF: 0.459 AC: 2209 AN: 4808

European-Finnish (FIN) AF: 0.456 AC: 4806 AN: 10544

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31451 AN: 67928

Other (OTH) AF: 0.544 AC: 1148 AN: 2112

Alfa AF: 0.482 Hom.: 12880

Bravo AF: 0.546

Asia WGS AF: 0.501 AC: 1739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.12
DANN	Benign	0.44
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs237476; hg19: chr20-48051382;