chr8-72578942-G-A

Variant names:

• chr8-72578942-G-A
• rs1431656
• NM_004770.3:c.579+10629G>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.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
• Publications: 5 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=-0.91).
• 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 rank	MANE	Protein	UniProt
KCNB2	NM_004770.3	c.579+10629G>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.579+10629G>A		intron_variant	Intron 2 of 2	1	NM_004770.3	ENSP00000430846.1

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

African (AFR) AF: 0.323 AC: 13386 AN: 41472

American (AMR) AF: 0.729 AC: 11133 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2314 AN: 3466

East Asian (EAS) AF: 0.688 AC: 3555 AN: 5168

South Asian (SAS) AF: 0.584 AC: 2813 AN: 4814

European-Finnish (FIN) AF: 0.740 AC: 7808 AN: 10552

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.727 AC: 49402 AN: 67958

Other (OTH) AF: 0.628 AC: 1323 AN: 2108

Alfa AF: 0.689 Hom.: 144356

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
PhyloP100		0.26
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: rs1431656; hg19: chr8-73491177;