8-72932080-A-G

Variant names:

• chr8-72932080-A-G
• rs7006287
• NM_004770.3:c.580-3855A>G

Variant summary

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

The NM_004770.3(KCNB2):​c.580-3855A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,878 control chromosomes in the GnomAD database, including 18,158 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 0.48 (18158 hom., cov: 31)
• Consequence: KCNB2 NM_004770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNB2	NM_004770.3	c.580-3855A>G		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.580-3855A>G		intron_variant	Intron 2 of 2	1	NM_004770.3	ENSP00000430846.1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 72923 AN: 151760 Hom.: 18148 Cov.: 31

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.480 AC: 72974 AN: 151878 Hom.: 18158 Cov.: 31 AF XY: 0.487 AC XY: 36128 AN XY: 74204

African (AFR) AF: 0.434 AC: 17941 AN: 41380

American (AMR) AF: 0.579 AC: 8842 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1475 AN: 3470

East Asian (EAS) AF: 0.887 AC: 4568 AN: 5148

South Asian (SAS) AF: 0.547 AC: 2638 AN: 4820

European-Finnish (FIN) AF: 0.456 AC: 4796 AN: 10520

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31146 AN: 67954

Other (OTH) AF: 0.479 AC: 1013 AN: 2114

Alfa AF: 0.462 Hom.: 4213

Bravo AF: 0.489

Asia WGS AF: 0.696 AC: 2419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.34
DANN	Benign	0.61
PhyloP100		-1.4
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: rs7006287; hg19: chr8-73844315;