1-6040585-C-T

Position:

chr1-6040585-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The ENST00000341524.6(KCNAB2):c.17C>T(p.Thr6Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000235 in 1,614,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

KCNAB2
ENST00000341524.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.26

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:

KCNAB2 (HGNC:):

KCNAB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21682492).

BP6

Variant 1-6040585-C-T is Benign according to our data. Variant chr1-6040585-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2638112.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
KCNAB2	NM_001199860.2 linkuse as main transcript	c.17C>T	p.Thr6Met	missense_variant	2/16	NP_001186789.1	Q13303-1A1PR14
KCNAB2	NM_001199861.2 linkuse as main transcript	c.17C>T	p.Thr6Met	missense_variant	2/16	NP_001186790.1	Q13303-1A1PR14
KCNAB2	NM_003636.4 linkuse as main transcript	c.17C>T	p.Thr6Met	missense_variant	2/16	NP_003627.1	Q13303-1A1PR14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
KCNAB2	ENST00000341524.6 linkuse as main transcript	c.17C>T	p.Thr6Met	missense_variant	2/17	1	ENSP00000340824.2	A0A5F9UN28
KCNAB2	ENST00000378097.6 linkuse as main transcript	c.17C>T	p.Thr6Met	missense_variant	2/16	1	ENSP00000367337.1	Q13303-1
KCNAB2	ENST00000352527.6 linkuse as main transcript	c.17C>T	p.Thr6Met	missense_variant	2/15	1	ENSP00000318772.1	Q13303-2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000597

AC:

AN:

251114

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461808

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000174

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

KCNAB2: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

T;T;.;T;.;T;T;T;.;T

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

.;.;.;D;D;D;.;D;D;.

M_CAP

Benign

0.068

MetaRNN

Benign

0.22

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.0

.;N;N;.;N;N;.;.;N;N

MutationTaster

Benign

0.91

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

PROVEAN

Benign

-0.83

N;N;N;D;N;N;N;N;.;N

REVEL

Benign

0.14

Sift

Pathogenic

0.0

D;D;D;D;D;D;D;D;.;D

Sift4G

Uncertain

0.042

D;T;D;D;D;T;T;D;D;T

Polyphen

0.99, 0.99

.;D;D;.;D;D;.;.;.;D

Vest4

0.54

MutPred

0.16

Loss of glycosylation at T6 (P = 0.0125);Loss of glycosylation at T6 (P = 0.0125);Loss of glycosylation at T6 (P = 0.0125);Loss of glycosylation at T6 (P = 0.0125);Loss of glycosylation at T6 (P = 0.0125);Loss of glycosylation at T6 (P = 0.0125);Loss of glycosylation at T6 (P = 0.0125);Loss of glycosylation at T6 (P = 0.0125);Loss of glycosylation at T6 (P = 0.0125);Loss of glycosylation at T6 (P = 0.0125);

MVP

0.55

ClinPred

0.20

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

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