rs1440355

Positions:

• chr8-72723452-G-A
• chr8-72723452-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000523207.2(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 ENST00000523207.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.760

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNB2	NM_004770.3	c.579+155139G>A		intron_variant		ENST00000523207.2	NP_004761.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNB2	ENST00000523207.2	c.579+155139G>A		intron_variant		1	NM_004770.3	ENSP00000430846	P1

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

Gnomad4 AFR AF: 0.905

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.701

Alfa AF: 0.692 Hom.: 14304

Bravo AF: 0.733

Asia WGS AF: 0.557 AC: 1941 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.33
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs1440355; hg19: chr8-73635687;