20-49365591-G-A

Position:

• chr20-49365591-G-A

Variant summary

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

The NM_004975.4(KCNB1):​c.*7392C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,146 control chromosomes in the GnomAD database, including 2,259 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 0.16 (2259 hom., cov: 32)
  • Exomes 𝑓: 0.083 (0 hom.)
• Consequence: KCNB1 NM_004975.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.865

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNB1	NM_004975.4	c.*7392C>T		3_prime_UTR_variant	2/2	ENST00000371741.6	NP_004966.1
KCNB1	XM_011528799.3	c.*7392C>T		3_prime_UTR_variant	3/3		XP_011527101.1
LOC105372649	XR_001754659.2	n.1201+33567G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNB1	ENST00000371741	c.*7392C>T		3_prime_UTR_variant	2/2	1	NM_004975.4	ENSP00000360806.3

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24718 AN: 152016 Hom.: 2260 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.0833 AC: 1 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 1 AN XY: 12

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.162 AC: 24709 AN: 152134 Hom.: 2259 Cov.: 32 AF XY: 0.161 AC XY: 12010 AN XY: 74380

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.134

Alfa AF: 0.138 Hom.: 814

Bravo AF: 0.168

Asia WGS AF: 0.112 AC: 390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.6
DANN	Benign	0.55

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: rs237450; hg19: chr20-47982128;