8-72539240-C-T

Variant names:

• chr8-72539240-C-T
• rs349358
• NM_004770.3:c.-94+1355C>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.-94+1355C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 152,170 control chromosomes in the GnomAD database, including 58,598 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 0.88 (58598 hom., cov: 31)
• Consequence: KCNB2 NM_004770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.514
• Publications: 15 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 (AFR) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNB2	NM_004770.3	c.-94+1355C>T		intron_variant	Intron 1 of 2	ENST00000523207.2	NP_004761.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNB2	ENST00000523207.2	c.-94+1355C>T		intron_variant	Intron 1 of 2	1	NM_004770.3	ENSP00000430846.1

Frequencies

GnomAD3 genomes AF: 0.875 AC: 133024 AN: 152050 Hom.: 58531 Cov.: 31

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.896

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.865

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

GnomAD4 genome AF: 0.875 AC: 133153 AN: 152170 Hom.: 58598 Cov.: 31 AF XY: 0.876 AC XY: 65181 AN XY: 74378

African (AFR) AF: 0.960 AC: 39881 AN: 41548

American (AMR) AF: 0.896 AC: 13703 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.852 AC: 2957 AN: 3472

East Asian (EAS) AF: 0.955 AC: 4949 AN: 5182

South Asian (SAS) AF: 0.794 AC: 3813 AN: 4804

European-Finnish (FIN) AF: 0.869 AC: 9198 AN: 10584

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.821 AC: 55790 AN: 67978

Other (OTH) AF: 0.867 AC: 1830 AN: 2110

Alfa AF: 0.835 Hom.: 29294

Bravo AF: 0.883

Asia WGS AF: 0.889 AC: 3086 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	6.4
DANN	Benign	0.46
PhyloP100		0.51
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: rs349358; hg19: chr8-73451475;