NM_004770.3:c.580-108918G>A

Variant names:

• chr8-72827017-G-A
• rs2919408
• NM_004770.3:c.580-108918G>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.580-108918G>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
• Publications: 4 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 (EAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004770.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNB2	NM_004770.3	MANE Select	c.580-108918G>A		intron	N/A	NP_004761.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNB2	ENST00000523207.2	TSL:1 MANE Select	c.580-108918G>A		intron	N/A	ENSP00000430846.1	Q92953

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

African (AFR) AF: 0.656 AC: 27188 AN: 41476

American (AMR) AF: 0.705 AC: 10773 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2181 AN: 3464

East Asian (EAS) AF: 0.907 AC: 4709 AN: 5190

South Asian (SAS) AF: 0.726 AC: 3506 AN: 4828

European-Finnish (FIN) AF: 0.644 AC: 6806 AN: 10570

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.639 AC: 43430 AN: 67956

Other (OTH) AF: 0.663 AC: 1401 AN: 2114

Alfa AF: 0.650 Hom.: 139051

Bravo AF: 0.666

Asia WGS AF: 0.801 AC: 2786 AN: 3478

ClinVar

ClinVar submissions

Significance: risk factor

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Colorectal cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.83
DANN	Benign	0.46
PhyloP100		-0.14
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: rs2919408; hg19: chr8-73739252;