1-6051641-G-C

Position:

chr1-6051641-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001199862.2(KCNAB2):c.105G>C(p.Gln35His) variant causes a missense change. The variant allele was found at a frequency of 0.000484 in 1,534,404 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00076 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00045 ( 7 hom. )

Consequence

KCNAB2
NM_001199862.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.78

Variant links:

Genes affected

KCNAB2 (HGNC:6229): (potassium voltage-gated channel subfamily A regulatory beta subunit 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, shaker-related subfamily. This member is one of the beta subunits, which are auxiliary proteins associating with functional Kv-alpha subunits. This member alters functional properties of the KCNA4 gene product. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Dec 2010]

KCNAB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009371251).

BP6

Variant 1-6051641-G-C is Benign according to our data. Variant chr1-6051641-G-C is described in ClinVar as [Benign]. Clinvar id is 3055395.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000454 (627/1382020) while in subpopulation AMR AF= 0.017 (605/35682). AF 95% confidence interval is 0.0158. There are 7 homozygotes in gnomad4_exome. There are 263 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 116 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNAB2	NM_001199862.2 linkuse as main transcript	c.105G>C	p.Gln35His	missense_variant	2/16	ENST00000378083.8	NP_001186791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNAB2	ENST00000378083.8 linkuse as main transcript	c.105G>C	p.Gln35His	missense_variant	2/16	2	NM_001199862.2	ENSP00000367323		Q13303-3

Frequencies

GnomAD3 genomes

AF:

0.000755

AC:

115

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00713

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00347

AC:

460

AN:

132672

Hom.:

AF XY:

0.00260

AC XY:

188

AN XY:

72312

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0186

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00146

GnomAD4 exome

AF:

0.000454

AC:

627

AN:

1382020

Hom.:

Cov.:

AF XY:

0.000386

AC XY:

263

AN XY:

681974

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.0170

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000278

Gnomad4 OTH exome

AF:

0.000312

GnomAD4 genome

AF:

0.000761

AC:

116

AN:

152384

Hom.:

Cov.:

AF XY:

0.000751

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00718

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000564

Hom.:

Bravo

AF:

0.00167

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KCNAB2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.69

M_CAP

Benign

0.074

MetaRNN

Benign

0.0094

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.85

D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.81

REVEL

Benign

0.048

Sift

Benign

0.042

Sift4G

Benign

0.54

Polyphen

0.73

Vest4

0.21

MutPred

0.33

Gain of methylation at R38 (P = 0.0811);

MVP

0.40

MPC

1.2

ClinPred

0.076

GERP RS

4.3

gMVP

0.59

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