rs237460

Positions:

• chr20-49416590-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004975.4(KCNB1):​c.568-41598G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,982 control chromosomes in the GnomAD database, including 22,486 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 (22486 hom., cov: 32)
• Consequence: KCNB1 NM_004975.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.40

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNB1	NM_004975.4	c.568-41598G>A		intron_variant		ENST00000371741.6
LOC105372649	XR_001754659.2	n.1202-10062C>T		intron_variant, non_coding_transcript_variant
KCNB1	XM_011528799.3	c.568-41598G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNB1	ENST00000371741.6	c.568-41598G>A		intron_variant		1	NM_004975.4	P1
KCNB1	ENST00000635465.1	c.568-41598G>A		intron_variant		1		P1
	ENST00000637341.1	n.207-6502C>T		intron_variant, non_coding_transcript_variant		5
KCNB1	ENST00000635878.1	c.96+65324G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80062 AN: 151864 Hom.: 22459 Cov.: 32

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.527 AC: 80138 AN: 151982 Hom.: 22486 Cov.: 32 AF XY: 0.524 AC XY: 38929 AN XY: 74264

Gnomad4 AFR AF: 0.731

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.534

Alfa AF: 0.490 Hom.: 2383

Bravo AF: 0.548

Asia WGS AF: 0.494 AC: 1714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.045
DANN	Benign	0.74

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: rs237460; hg19: chr20-48033127;