rs237477

Positions:

• chr20-49440911-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.567+41003G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 152,196 control chromosomes in the GnomAD database, including 40,419 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 0.72 (40395 hom., cov: 32)
  • Exomes 𝑓: 0.71 (24 hom.)
• Consequence: KCNB1 NM_004975.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNB1	NM_004975.4	c.567+41003G>A		intron_variant		ENST00000371741.6
KCNB1	XM_011528799.3	c.567+41003G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNB1	ENST00000371741.6	c.567+41003G>A		intron_variant		1	NM_004975.4	P1
KCNB1	ENST00000635465.1	c.567+41003G>A		intron_variant		1		P1
	ENST00000637341.1	n.945C>T		non_coding_transcript_exon_variant	8/8	5
KCNB1	ENST00000635878.1	c.96+41003G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108658 AN: 151982 Hom.: 40342 Cov.: 32

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.726

GnomAD4 exome AF: 0.713 AC: 67 AN: 94 Hom.: 24 Cov.: 0 AF XY: 0.722 AC XY: 52 AN XY: 72

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.750

Gnomad4 NFE exome AF: 0.718

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.715 AC: 108764 AN: 152102 Hom.: 40395 Cov.: 32 AF XY: 0.714 AC XY: 53081 AN XY: 74334

Gnomad4 AFR AF: 0.930

Gnomad4 AMR AF: 0.708

Gnomad4 ASJ AF: 0.720

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.718

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.719

Alfa AF: 0.642 Hom.: 41587

Bravo AF: 0.734

Asia WGS AF: 0.709 AC: 2466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.41

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: rs237477; hg19: chr20-48057448;