8-72722637-T-C

Position:

• chr8-72722637-T-C

Variant summary

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

The NM_004770.3(KCNB2):​c.579+154324T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,088 control chromosomes in the GnomAD database, including 36,871 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 0.69 (36871 hom., cov: 32)
• Consequence: KCNB2 NM_004770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNB2	NM_004770.3	c.579+154324T>C		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+154324T>C		intron_variant		1	NM_004770.3	ENSP00000430846.1

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104197 AN: 151968 Hom.: 36815 Cov.: 32

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.686 AC: 104316 AN: 152088 Hom.: 36871 Cov.: 32 AF XY: 0.675 AC XY: 50173 AN XY: 74314

Gnomad4 AFR AF: 0.847

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.667

Alfa AF: 0.659 Hom.: 14958

Bravo AF: 0.694

Asia WGS AF: 0.519 AC: 1809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.34

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: rs2247329; hg19: chr8-73634872;