20-49381992-C-T

Variant names:

• chr20-49381992-C-T
• rs13433293
• NM_004975.4:c.568-7000G>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.568-7000G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,032 control chromosomes in the GnomAD database, including 3,795 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 0.21 (3795 hom., cov: 31)
• Consequence: KCNB1 NM_004975.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520
• Publications: 2 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 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.568-7000G>A		intron	N/A	NP_004966.1	Q14721

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNB1	ENST00000371741.6	TSL:1 MANE Select	c.568-7000G>A		intron	N/A	ENSP00000360806.3	Q14721
	KCNB1	ENST00000635465.1	TSL:1	c.568-7000G>A		intron	N/A	ENSP00000489193.1	Q14721
	KCNB1	ENST00000635878.1	TSL:5	c.97-82609G>A		intron	N/A	ENSP00000489908.1	A0A1B0GU02

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31452 AN: 151914 Hom.: 3784 Cov.: 31

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.0255

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.207 AC: 31484 AN: 152032 Hom.: 3795 Cov.: 31 AF XY: 0.204 AC XY: 15163 AN XY: 74338

African (AFR) AF: 0.317 AC: 13111 AN: 41416

American (AMR) AF: 0.152 AC: 2327 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 960 AN: 3466

East Asian (EAS) AF: 0.0251 AC: 130 AN: 5174

South Asian (SAS) AF: 0.167 AC: 804 AN: 4820

European-Finnish (FIN) AF: 0.124 AC: 1313 AN: 10586

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12142 AN: 67978

Other (OTH) AF: 0.208 AC: 437 AN: 2106

Alfa AF: 0.149 Hom.: 510

Bravo AF: 0.211

Asia WGS AF: 0.120 AC: 418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.51
PhyloP100		-0.52
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: rs13433293; hg19: chr20-47998529;