rs4143635

Variant names:

• chr8-72797068-G-A
• rs4143635
• NM_004770.3:c.580-138867G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004770.3(KCNB2):​c.580-138867G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,020 control chromosomes in the GnomAD database, including 2,278 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 0.15 (2278 hom., cov: 32)
• Consequence: KCNB2 NM_004770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176
• Publications: 3 publications found

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]

KCNB2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNB2	NM_004770.3	c.580-138867G>A		intron_variant	Intron 2 of 2	ENST00000523207.2	NP_004761.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNB2	ENST00000523207.2	c.580-138867G>A		intron_variant	Intron 2 of 2	1	NM_004770.3	ENSP00000430846.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23188 AN: 151902 Hom.: 2282 Cov.: 32

Gnomad AFR AF: 0.0348

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.152 AC: 23179 AN: 152020 Hom.: 2278 Cov.: 32 AF XY: 0.158 AC XY: 11714 AN XY: 74260

African (AFR) AF: 0.0347 AC: 1440 AN: 41504

American (AMR) AF: 0.154 AC: 2351 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 668 AN: 3466

East Asian (EAS) AF: 0.278 AC: 1437 AN: 5166

South Asian (SAS) AF: 0.210 AC: 1012 AN: 4812

European-Finnish (FIN) AF: 0.272 AC: 2872 AN: 10540

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12764 AN: 67960

Other (OTH) AF: 0.160 AC: 337 AN: 2108

Alfa AF: 0.177 Hom.: 4070

Bravo AF: 0.142

Asia WGS AF: 0.236 AC: 823 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.60
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4143635; hg19: chr8-73709303;