8-72605051-A-G

Variant names:

• chr8-72605051-A-G
• rs4738269
• NM_004770.3:c.579+36738A>G

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+36738A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,188 control chromosomes in the GnomAD database, including 2,665 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 0.17 (2665 hom., cov: 33)
• Consequence: KCNB2 NM_004770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 3 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=-0.53).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 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.579+36738A>G		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.579+36738A>G		intron	N/A	ENSP00000430846.1	Q92953

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26073 AN: 152070 Hom.: 2662 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.171 AC: 26086 AN: 152188 Hom.: 2665 Cov.: 33 AF XY: 0.173 AC XY: 12849 AN XY: 74392

African (AFR) AF: 0.137 AC: 5700 AN: 41550

American (AMR) AF: 0.172 AC: 2627 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3470

East Asian (EAS) AF: 0.513 AC: 2653 AN: 5168

South Asian (SAS) AF: 0.229 AC: 1102 AN: 4820

European-Finnish (FIN) AF: 0.193 AC: 2043 AN: 10578

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10838 AN: 68012

Other (OTH) AF: 0.186 AC: 393 AN: 2112

Alfa AF: 0.161 Hom.: 2691

Bravo AF: 0.170

Asia WGS AF: 0.337 AC: 1169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.54
DANN	Benign	0.74
PhyloP100		-1.7
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: rs4738269; hg19: chr8-73517286;