rs4809745

Variant names:

• chr20-49471334-G-A
• rs4809745
• NM_004975.4:c.567+10580C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-49471334-G-A
• chr20-49471334-G-C

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+10580C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 152,060 control chromosomes in the GnomAD database, including 414 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 0.065 (414 hom., cov: 30)
• Consequence: KCNB1 NM_004975.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 4 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNB1	NM_004975.4	c.567+10580C>T		intron_variant	Intron 1 of 1	ENST00000371741.6	NP_004966.1
KCNB1	XM_011528799.3	c.567+10580C>T		intron_variant	Intron 2 of 2		XP_011527101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNB1	ENST00000371741.6	c.567+10580C>T		intron_variant	Intron 1 of 1	1	NM_004975.4	ENSP00000360806.3
KCNB1	ENST00000635465.1	c.567+10580C>T		intron_variant	Intron 2 of 2	1		ENSP00000489193.1
KCNB1	ENST00000635878.1	c.96+10580C>T		intron_variant	Intron 1 of 2	5		ENSP00000489908.1
KCNB1	ENST00000636950.1	n.87+10580C>T		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.0646 AC: 9810 AN: 151944 Hom.: 414 Cov.: 30

Gnomad AFR AF: 0.0152

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0827

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0958

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0806

Gnomad OTH AF: 0.0603

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

GnomAD4 genome AF: 0.0645 AC: 9810 AN: 152060 Hom.: 414 Cov.: 30 AF XY: 0.0660 AC XY: 4905 AN XY: 74316

African (AFR) AF: 0.0152 AC: 630 AN: 41476

American (AMR) AF: 0.0826 AC: 1263 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3470

East Asian (EAS) AF: 0.120 AC: 618 AN: 5162

South Asian (SAS) AF: 0.0960 AC: 461 AN: 4800

European-Finnish (FIN) AF: 0.102 AC: 1079 AN: 10582

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0807 AC: 5482 AN: 67972

Other (OTH) AF: 0.0597 AC: 126 AN: 2110

Alfa AF: 0.0704 Hom.: 758

Bravo AF: 0.0622

Asia WGS AF: 0.0860 AC: 297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.071
DANN	Benign	0.94
PhyloP100		-1.8
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: rs4809745; hg19: chr20-48087871;