chr17-7445306-A-G

Position:

chr17-7445306-A-G

Variant summary

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

The NM_000747.3(CHRNB1):c.95A>G(p.Glu32Gly) variant causes a missense change. The variant allele was found at a frequency of 0.319 in 1,612,188 control chromosomes in the GnomAD database, including 91,748 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 6030 hom., cov: 32)

Exomes 𝑓: 0.33 ( 85718 hom. )

Consequence

CHRNB1
NM_000747.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 6.06

Variant links:

Genes affected

CHRNB1 (HGNC:1961): (cholinergic receptor nicotinic beta 1 subunit) The muscle acetylcholine receptor is composed of five subunits: two alpha subunits and one beta, one gamma, and one delta subunit. This gene encodes the beta subunit of the acetylcholine receptor. The acetylcholine receptor changes conformation upon acetylcholine binding leading to the opening of an ion-conducting channel across the plasma membrane. Mutations in this gene are associated with slow-channel congenital myasthenic syndrome. [provided by RefSeq, Jul 2008]

CHRNB1 links:

ENSG00000272884 (HGNC:):

ENSG00000272884 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=0.0031630695).

BP6

Variant 17-7445306-A-G is Benign according to our data. Variant chr17-7445306-A-G is described in ClinVar as [Benign]. Clinvar id is 128754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7445306-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNB1	NM_000747.3 linkuse as main transcript	c.95A>G	p.Glu32Gly	missense_variant	2/11	ENST00000306071.7	NP_000738.2	P11230-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB1	ENST00000306071.7 linkuse as main transcript	c.95A>G	p.Glu32Gly	missense_variant	2/11	1	NM_000747.3	ENSP00000304290.2		P11230-1

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36844

AN:

151998

Hom.:

6033

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0631

Gnomad AMI

AF:

0.396

Gnomad AMR

AF:

0.233

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.00251

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.275

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.367

Gnomad OTH

AF:

0.282

GnomAD3 exomes

AF:

0.248

AC:

60334

AN:

243398

Hom.:

9565

AF XY:

0.254

AC XY:

33759

AN XY:

132924

show subpopulations

Gnomad AFR exome

AF:

0.0517

Gnomad AMR exome

AF:

0.164

Gnomad ASJ exome

AF:

0.350

Gnomad EAS exome

AF:

0.000658

Gnomad SAS exome

AF:

0.118

Gnomad FIN exome

AF:

0.272

Gnomad NFE exome

AF:

0.364

Gnomad OTH exome

AF:

0.291

GnomAD4 exome

AF:

0.327

AC:

478142

AN:

1460072

Hom.:

85718

Cov.:

AF XY:

0.323

AC XY:

234714

AN XY:

726302

show subpopulations

Gnomad4 AFR exome

AF:

0.0523

Gnomad4 AMR exome

AF:

0.171

Gnomad4 ASJ exome

AF:

0.357

Gnomad4 EAS exome

AF:

0.000655

Gnomad4 SAS exome

AF:

0.121

Gnomad4 FIN exome

AF:

0.278

Gnomad4 NFE exome

AF:

0.373

Gnomad4 OTH exome

AF:

0.302

GnomAD4 genome

AF:

0.242

AC:

36826

AN:

152116

Hom.:

6030

Cov.:

AF XY:

0.234

AC XY:

17413

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0630

Gnomad4 AMR

AF:

0.233

Gnomad4 ASJ

AF:

0.355

Gnomad4 EAS

AF:

0.00252

Gnomad4 SAS

AF:

0.112

Gnomad4 FIN

AF:

0.275

Gnomad4 NFE

AF:

0.367

Gnomad4 OTH

AF:

0.279

Alfa

AF:

0.352

Hom.:

12287

Bravo

AF:

0.231

TwinsUK

AF:

0.379

AC:

1404

ALSPAC

AF:

0.369

AC:

1422

ESP6500AA

AF:

0.0641

AC:

282

ESP6500EA

AF:

0.354

AC:

3042

ExAC

AF:

0.244

AC:

29534

Asia WGS

AF:

0.0540

AC:

186

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Feb 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 07, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Congenital myasthenic syndrome 2A

Benign:2

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Congenital myasthenic syndrome 4C

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

T;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.95

MetaRNN

Benign

0.0032

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-2.6

D;.

REVEL

Uncertain

0.32

Sift

Benign

0.26

T;.

Sift4G

Benign

0.18

T;T

Polyphen

0.77

P;.

Vest4

0.11

MPC

0.70

ClinPred

0.037

GERP RS

5.4

Varity_R

0.24

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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