rs2253667

chr8-72740413-G-Achr8-72740413-G-T

Variant summary

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

The NM_004770.3(KCNB2):c.579+172100G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,066 control chromosomes in the GnomAD database, including 3,382 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 0.18 (3382 hom., cov: 32)
• Consequence: KCNB2 NM_004770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNB2	NM_004770.3	c.579+172100G>A		intron_variant		ENST00000523207.2
LOC101926908	NR_110656.1	n.57+8312G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNB2	ENST00000523207.2	c.579+172100G>A		intron_variant		1	NM_004770.3	P1
	ENST00000519427.1	n.57+8312G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27882 AN: 151948 Hom.: 3373 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.184 AC: 27927 AN: 152066 Hom.: 3382 Cov.: 32 AF XY: 0.183 AC XY: 13635 AN XY: 74358

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.169

Alfa AF: 0.144 Hom.: 264

Bravo AF: 0.189

Asia WGS AF: 0.209 AC: 728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.0
Dann	Benign	0.76

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: rs2253667; hg19: chr8-73652648;