dbSNP rs529702052: KCNAB2:p.Gln35His (chr1-6051641-G-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00076 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00045 ( 7 hom. )

Consequence

KCNAB2
NM_001199862.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.78

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 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 Likely_benign. ClinVar VariationId is 3055395.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 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 GnomAdExome4. There are 263 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 116 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199862.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCNAB2	NM_001199862.2	MANE Select	c.105G>C	p.Gln35His	missense	Exon 2 of 16	NP_001186791.1	Q13303-3
KCNAB2	NM_001199860.2		c.119+9769G>C		intron	N/A	NP_001186789.1	Q13303-1
KCNAB2	NM_001199861.2		c.119+9769G>C		intron	N/A	NP_001186790.1	Q13303-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCNAB2	ENST00000378083.8	TSL:2 MANE Select	c.105G>C	p.Gln35His	missense	Exon 2 of 16	ENSP00000367323.3	Q13303-3
KCNAB2	ENST00000341524.6	TSL:1	c.119+9769G>C		intron	N/A	ENSP00000340824.2	A0A5F9UN28
KCNAB2	ENST00000378097.6	TSL:1	c.119+9769G>C		intron	N/A	ENSP00000367337.1	Q13303-1

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

GnomAD2 exomes

AF:

0.00347

AC:

460

AN:

132672

AF XY:

0.00260

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 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

African (AFR)

AF:

0.0000317

AC:

AN:

31540

American (AMR)

AF:

0.0170

AC:

605

AN:

35682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25162

East Asian (EAS)

AF:

0.00

AC:

AN:

35728

South Asian (SAS)

AF:

0.00

AC:

AN:

79140

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33738

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4644

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1078636

Other (OTH)

AF:

0.000312

AC:

AN:

57750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

113

151

189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000761

AC:

116

AN:

152384

Hom.:

Cov.:

AF XY:

0.000751

AC XY:

AN XY:

74518

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41596

American (AMR)

AF:

0.00718

AC:

110

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000564

Hom.:

Bravo

AF:

0.00167

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

KCNAB2-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

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

PhyloP100

3.8

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

Mutation Taster

=76/24

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over