rs2128158

chr8-72917865-G-Achr8-72917865-G-C

Variant summary

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

The NM_004770.3(KCNB2):c.580-18070G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,146 control chromosomes in the GnomAD database, including 1,304 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 0.12 (1304 hom., cov: 33)
• Consequence: KCNB2 NM_004770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800

Genes affected

KCNB2 (HGNC:6232): (potassium voltage-gated channel subfamily B member 2) 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. The gene is expressed in gastrointestinal smooth muscle cells. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNB2	NM_004770.3	c.580-18070G>A		intron_variant		ENST00000523207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNB2	ENST00000523207.2	c.580-18070G>A		intron_variant		1	NM_004770.3	P1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18316 AN: 152028 Hom.: 1303 Cov.: 33

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0791

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0828

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0973

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.121 AC: 18344 AN: 152146 Hom.: 1304 Cov.: 33 AF XY: 0.119 AC XY: 8844 AN XY: 74396

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.0789

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.00367

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0828

Gnomad4 NFE AF: 0.0974

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0956 Hom.: 663

Bravo AF: 0.122

Asia WGS AF: 0.0510 AC: 176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	6.5
Dann	Benign	0.78

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: rs2128158; hg19: chr8-73830100;