8-72576736-C-T

Variant names:

• chr8-72576736-C-T
• rs349335
• NM_004770.3:c.579+8423C>T

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+8423C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 152,222 control chromosomes in the GnomAD database, including 61,126 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 0.89 (61126 hom., cov: 32)
• Consequence: KCNB2 NM_004770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.583
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 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+8423C>T		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+8423C>T		intron	N/A	ENSP00000430846.1	Q92953

Frequencies

GnomAD3 genomes AF: 0.894 AC: 136053 AN: 152104 Hom.: 61066 Cov.: 32

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.878

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

GnomAD4 genome AF: 0.895 AC: 136172 AN: 152222 Hom.: 61126 Cov.: 32 AF XY: 0.894 AC XY: 66541 AN XY: 74412

African (AFR) AF: 0.964 AC: 40055 AN: 41560

American (AMR) AF: 0.903 AC: 13803 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 3037 AN: 3470

East Asian (EAS) AF: 0.957 AC: 4951 AN: 5174

South Asian (SAS) AF: 0.818 AC: 3937 AN: 4814

European-Finnish (FIN) AF: 0.886 AC: 9385 AN: 10598

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.855 AC: 58117 AN: 68004

Other (OTH) AF: 0.880 AC: 1860 AN: 2114

Alfa AF: 0.865 Hom.: 104663

Bravo AF: 0.900

Asia WGS AF: 0.899 AC: 3125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.8
DANN	Benign	0.61
PhyloP100		0.58
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: rs349335; hg19: chr8-73488971;