chr8-72605051-A-G

Position:

• chr8-72605051-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.53).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNB2	NM_004770.3	c.579+36738A>G		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+36738A>G		intron_variant		1	NM_004770.3	ENSP00000430846	P1

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

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.513

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.186

Alfa AF: 0.162 Hom.: 2044

Bravo AF: 0.170

Asia WGS AF: 0.337 AC: 1169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.54
DANN	Benign	0.74

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: rs4738269; hg19: chr8-73517286;