rs552068

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
KCNB1	NM_004975.4	c.567+10453T>G		intron_variant		ENST00000371741.6	NP_004966.1
KCNB1	XM_011528799.3	c.567+10453T>G		intron_variant			XP_011527101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNB1	ENST00000371741.6	c.567+10453T>G		intron_variant		1	NM_004975.4	ENSP00000360806	P1
KCNB1	ENST00000635465.1	c.567+10453T>G		intron_variant		1		ENSP00000489193	P1
KCNB1	ENST00000635878.1	c.96+10453T>G		intron_variant		5		ENSP00000489908
KCNB1	ENST00000636950.1	n.87+10453T>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.684

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.647

Alfa AF: 0.628 Hom.: 14975

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

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

LitVar

Other links and lift over

dbSNP: rs552068; hg19: chr20-48087998;