rs11782342

Variant names:

• chr8-72872602-G-A
• rs11782342
• NM_004770.3:c.580-63333G>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.580-63333G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,186 control chromosomes in the GnomAD database, including 2,377 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 (2377 hom., cov: 33)
• Consequence: KCNB2 NM_004770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.672
• 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

KCNB2-AS1 (HGNC:58256):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNB2	NM_004770.3	c.580-63333G>A		intron_variant	Intron 2 of 2	ENST00000523207.2	NP_004761.2
KCNB2-AS1	NR_199040.1	n.2803C>T		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNB2	ENST00000523207.2	c.580-63333G>A		intron_variant	Intron 2 of 2	1	NM_004770.3	ENSP00000430846.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23280 AN: 152068 Hom.: 2377 Cov.: 33

Gnomad AFR AF: 0.0394

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0496

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.153 AC: 23287 AN: 152186 Hom.: 2377 Cov.: 33 AF XY: 0.152 AC XY: 11319 AN XY: 74390

African (AFR) AF: 0.0392 AC: 1631 AN: 41560

American (AMR) AF: 0.125 AC: 1910 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 672 AN: 3470

East Asian (EAS) AF: 0.0499 AC: 258 AN: 5170

South Asian (SAS) AF: 0.124 AC: 597 AN: 4822

European-Finnish (FIN) AF: 0.214 AC: 2267 AN: 10600

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15407 AN: 67964

Other (OTH) AF: 0.150 AC: 317 AN: 2114

Alfa AF: 0.175 Hom.: 448

Bravo AF: 0.141

Asia WGS AF: 0.105 AC: 363 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.4
DANN	Benign	0.74
PhyloP100		0.67
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: rs11782342; hg19: chr8-73784837;