8-72584353-A-G

Position:

• chr8-72584353-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+16040A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 152,028 control chromosomes in the GnomAD database, including 43,351 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 0.75 (43351 hom., cov: 31)
• Consequence: KCNB2 NM_004770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.383

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNB2	NM_004770.3	c.579+16040A>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+16040A>G		intron_variant		1	NM_004770.3	ENSP00000430846.1

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114438 AN: 151910 Hom.: 43307 Cov.: 31

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.735

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

GnomAD4 genome AF: 0.753 AC: 114534 AN: 152028 Hom.: 43351 Cov.: 31 AF XY: 0.752 AC XY: 55905 AN XY: 74308

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.787

Gnomad4 ASJ AF: 0.736

Gnomad4 EAS AF: 0.687

Gnomad4 SAS AF: 0.603

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.739

Gnomad4 OTH AF: 0.734

Alfa AF: 0.719 Hom.: 15258

Bravo AF: 0.759

Asia WGS AF: 0.699 AC: 2429 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.30

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: rs1542709; hg19: chr8-73496588;