Variant 8-72935904-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004770.3(KCNB2):c.580-31A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0878 in 1,539,402 control chromosomes in the GnomAD database, including 22,968 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 2755 hom., cov: 32)

Exomes 𝑓: 0.085 ( 20213 hom. )

Consequence

KCNB2
NM_004770.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0660

Variant links:

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]

KCNB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 8-72935904-A-T is Benign according to our data. Variant chr8-72935904-A-T is described in ClinVar as [Benign]. Clinvar id is 1263527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNB2	NM_004770.3 linkuse as main transcript	c.580-31A>T		intron_variant		ENST00000523207.2	NP_004761.2	Q92953
KCNB2	XM_017013982.2 linkuse as main transcript	c.-156-31A>T		intron_variant			XP_016869471.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNB2	ENST00000523207.2 linkuse as main transcript	c.580-31A>T		intron_variant		1	NM_004770.3	ENSP00000430846.1		Q92953

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16619

AN:

152052

Hom.:

2753

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0984

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.0542

Gnomad EAS

AF:

0.787

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.0370

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0353

Gnomad OTH

AF:

0.104

GnomAD3 exomes

AF:

0.177

AC:

42352

AN:

239952

Hom.:

9727

AF XY:

0.167

AC XY:

21526

AN XY:

129030

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.376

Gnomad ASJ exome

AF:

0.0582

Gnomad EAS exome

AF:

0.789

Gnomad SAS exome

AF:

0.268

Gnomad FIN exome

AF:

0.0399

Gnomad NFE exome

AF:

0.0382

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.0855

AC:

118596

AN:

1387232

Hom.:

20213

Cov.:

AF XY:

0.0885

AC XY:

61234

AN XY:

691710

show subpopulations

Gnomad4 AFR exome

AF:

0.0958

Gnomad4 AMR exome

AF:

0.360

Gnomad4 ASJ exome

AF:

0.0578

Gnomad4 EAS exome

AF:

0.784

Gnomad4 SAS exome

AF:

0.262

Gnomad4 FIN exome

AF:

0.0403

Gnomad4 NFE exome

AF:

0.0354

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.109

AC:

16636

AN:

152170

Hom.:

2755

Cov.:

AF XY:

0.120

AC XY:

8895

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0983

Gnomad4 AMR

AF:

0.254

Gnomad4 ASJ

AF:

0.0542

Gnomad4 EAS

AF:

0.788

Gnomad4 SAS

AF:

0.290

Gnomad4 FIN

AF:

0.0370

Gnomad4 NFE

AF:

0.0353

Gnomad4 OTH

AF:

0.105

Alfa

AF:

0.0336

Hom.:

Bravo

AF:

0.126

Asia WGS

AF:

0.456

AC:

1581

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

-0.66

CADD

Benign

DANN

Benign

0.89

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over