rs552068

Variant names:

• chr20-49471461-A-C
• rs552068
• NM_004975.4:c.567+10453T>G

Your query was ambiguous. Multiple possible variants found:

• chr20-49471461-A-C
• chr20-49471461-A-G

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+10453T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,770 control chromosomes in the GnomAD database, including 29,095 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 0.62 (29095 hom., cov: 30)
• Consequence: KCNB1 NM_004975.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNB1	NM_004975.4	c.567+10453T>G		intron_variant	Intron 1 of 1	ENST00000371741.6	NP_004966.1
KCNB1	XM_011528799.3	c.567+10453T>G		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+10453T>G		intron_variant	Intron 1 of 1	1	NM_004975.4	ENSP00000360806.3
KCNB1	ENST00000635465.1	c.567+10453T>G		intron_variant	Intron 2 of 2	1		ENSP00000489193.1
KCNB1	ENST00000635878.1	c.96+10453T>G		intron_variant	Intron 1 of 2	5		ENSP00000489908.1
KCNB1	ENST00000636950.1	n.87+10453T>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93470 AN: 151654 Hom.: 29058 Cov.: 30

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.710

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.616 AC: 93547 AN: 151770 Hom.: 29095 Cov.: 30 AF XY: 0.614 AC XY: 45542 AN XY: 74150

African (AFR) AF: 0.631 AC: 26080 AN: 41362

American (AMR) AF: 0.524 AC: 7999 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2336 AN: 3468

East Asian (EAS) AF: 0.451 AC: 2330 AN: 5168

South Asian (SAS) AF: 0.684 AC: 3276 AN: 4792

European-Finnish (FIN) AF: 0.586 AC: 6172 AN: 10534

Middle Eastern (MID) AF: 0.712 AC: 208 AN: 292

European-Non Finnish (NFE) AF: 0.640 AC: 43427 AN: 67874

Other (OTH) AF: 0.647 AC: 1361 AN: 2104

Alfa AF: 0.628 Hom.: 20920

Bravo AF: 0.609

Asia WGS AF: 0.547 AC: 1897 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.0
DANN	Benign	0.82
PhyloP100		1.3
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: rs552068; hg19: chr20-48087998;