8-72827017-G-A

Position:

• chr8-72827017-G-A

Variant summary

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

The NM_004770.3(KCNB2):​c.580-108918G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,088 control chromosomes in the GnomAD database, including 33,613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: 𝑓 0.66 (33613 hom., cov: 33)
• Consequence: KCNB2 NM_004770.3 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -0.140

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNB2	NM_004770.3	c.580-108918G>A		intron_variant		ENST00000523207.2	NP_004761.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNB2	ENST00000523207.2	c.580-108918G>A		intron_variant		1	NM_004770.3	ENSP00000430846.1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100659 AN: 151970 Hom.: 33590 Cov.: 33

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.662 AC: 100733 AN: 152088 Hom.: 33613 Cov.: 33 AF XY: 0.664 AC XY: 49395 AN XY: 74354

Gnomad4 AFR AF: 0.656

Gnomad4 AMR AF: 0.705

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.907

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.639

Gnomad4 OTH AF: 0.663

Alfa AF: 0.648 Hom.: 66160

Bravo AF: 0.666

Asia WGS AF: 0.801 AC: 2786 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Colorectal cancer Other:1

risk factor, no assertion criteria provided

case-control

Colorectal Cancer Research Lab, Singapore General Hospital

Mar 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.83
DANN	Benign	0.46

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: rs2919408; hg19: chr8-73739252;