8-72723452-G-A

Variant names:

• chr8-72723452-G-A
• rs1440355
• NM_004770.3:c.579+155139G>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+155139G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,090 control chromosomes in the GnomAD database, including 41,126 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 0.72 (41126 hom., cov: 32)
• Consequence: KCNB2 NM_004770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.760
• Publications: 2 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNB2	NM_004770.3	MANE Select	c.579+155139G>A		intron	N/A	NP_004761.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNB2	ENST00000523207.2	TSL:1 MANE Select	c.579+155139G>A		intron	N/A	ENSP00000430846.1

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110006 AN: 151972 Hom.: 41065 Cov.: 32

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.724 AC: 110132 AN: 152090 Hom.: 41126 Cov.: 32 AF XY: 0.716 AC XY: 53189 AN XY: 74338

African (AFR) AF: 0.905 AC: 37563 AN: 41522

American (AMR) AF: 0.617 AC: 9413 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2065 AN: 3470

East Asian (EAS) AF: 0.434 AC: 2238 AN: 5158

South Asian (SAS) AF: 0.579 AC: 2784 AN: 4810

European-Finnish (FIN) AF: 0.633 AC: 6689 AN: 10562

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47099 AN: 67992

Other (OTH) AF: 0.701 AC: 1480 AN: 2112

Alfa AF: 0.695 Hom.: 23685

Bravo AF: 0.733

Asia WGS AF: 0.557 AC: 1941 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.33
DANN	Benign	0.51
PhyloP100		-0.76
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: rs1440355; hg19: chr8-73635687;