8-72567488-A-G

Position:

• chr8-72567488-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004770.3(KCNB2):​c.-93-154A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 151,976 control chromosomes in the GnomAD database, including 25,221 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.55 (25221 hom., cov: 31)
• Consequence: KCNB2 NM_004770.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.48

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 8-72567488-A-G is Benign according to our data. Variant chr8-72567488-A-G is described in ClinVar as [Benign]. Clinvar id is 1297797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNB2	NM_004770.3	c.-93-154A>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.-93-154A>G		intron_variant		1	NM_004770.3	ENSP00000430846.1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83039 AN: 151858 Hom.: 25196 Cov.: 31

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.547 AC: 83096 AN: 151976 Hom.: 25221 Cov.: 31 AF XY: 0.551 AC XY: 40956 AN XY: 74282

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.522

Gnomad4 FIN AF: 0.700

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.558

Alfa AF: 0.590 Hom.: 5067

Bravo AF: 0.534

Asia WGS AF: 0.513 AC: 1783 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.022
DANN	Benign	0.46

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: rs2451034; hg19: chr8-73479723;