rs1431656

Positions:

• chr8-72578942-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.579+10629G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 152,010 control chromosomes in the GnomAD database, including 30,740 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 0.61 (30740 hom., cov: 32)
• Consequence: KCNB2 NM_004770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259

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 (AMR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNB2	NM_004770.3	c.579+10629G>A		intron_variant		ENST00000523207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNB2	ENST00000523207.2	c.579+10629G>A		intron_variant		1	NM_004770.3	P1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92539 AN: 151892 Hom.: 30729 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.609 AC: 92573 AN: 152010 Hom.: 30740 Cov.: 32 AF XY: 0.611 AC XY: 45379 AN XY: 74290

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.729

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.727

Gnomad4 OTH AF: 0.628

Alfa AF: 0.705 Hom.: 71071

Bravo AF: 0.598

Asia WGS AF: 0.664 AC: 2306 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.22

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: rs1431656; hg19: chr8-73491177;