3-156120699-G-C

Position:

chr3-156120699-G-C

Variant summary

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

The NM_172160.3(KCNAB1):c.88G>C(p.Gly30Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00284 in 1,614,236 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 71 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 73 hom. )

Consequence

KCNAB1
NM_172160.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.712

Variant links:

Genes affected

KCNAB1 (HGNC:6228): (potassium voltage-gated channel subfamily A regulatory beta subunit 1) Potassium 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 includes distinct isoforms which are encoded by alternatively spliced transcript variants of this gene. Some of these isoforms are beta subunits, which form heteromultimeric complexes with alpha subunits and modulate the activity of the pore-forming alpha subunits. [provided by RefSeq, Apr 2015]

KCNAB1 links:

KCNAB1 (HGNC:):

KCNAB1 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 (MetaRNN=0.002829671).

BP6

Variant 3-156120699-G-C is Benign according to our data. Variant chr3-156120699-G-C is described in ClinVar as [Benign]. Clinvar id is 789724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.051 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNAB1	NM_172160.3 linkuse as main transcript	c.88G>C	p.Gly30Arg	missense_variant	1/14	ENST00000490337.6	NP_751892.1	Q14722-1
KCNAB1	NM_001308217.1 linkuse as main transcript	c.88G>C	p.Gly30Arg	missense_variant	1/13		NP_001295146.1	Q14722B7Z8E5
KCNAB1	XM_017007174.3 linkuse as main transcript	c.88G>C	p.Gly30Arg	missense_variant	1/9		XP_016862663.1
KCNAB1	XM_017007171.3 linkuse as main transcript	c.29+2360G>C		intron_variant			XP_016862660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNAB1	ENST00000490337.6 linkuse as main transcript	c.88G>C	p.Gly30Arg	missense_variant	1/14	1	NM_172160.3	ENSP00000419952.1		Q14722-1

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

2279

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0529

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

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:

0.000103

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00374

AC:

940

AN:

251474

Hom.:

AF XY:

0.00270

AC XY:

367

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.0514

Gnomad AMR exome

AF:

0.00254

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:

0.0000615

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00157

AC:

2302

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

994

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0567

Gnomad4 AMR exome

AF:

0.00257

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000261

Gnomad4 OTH exome

AF:

0.00391

GnomAD4 genome

AF:

0.0150

AC:

2283

AN:

152342

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1060

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0528

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.000691

Hom.:

Bravo

AF:

0.0173

ESP6500AA

AF:

0.0533

AC:

235

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00451

AC:

547

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.0000593

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.11

T;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.0028

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.74

N;N

REVEL

Benign

0.072

Sift

Benign

0.041

D;D

Sift4G

Benign

0.085

T;T

Polyphen

0.010

B;B

Vest4

0.25

MutPred

0.22

Gain of MoRF binding (P = 0.0245);Gain of MoRF binding (P = 0.0245);

MVP

0.31

MPC

0.67

ClinPred

0.014

GERP RS

-2.0

Varity_R

0.11

gMVP

0.22

Splicing

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