rs76001008

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000747.3(CHRNB1):c.821-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 1,605,916 control chromosomes in the GnomAD database, including 321 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 26 hom., cov: 30)

Exomes 𝑓: 0.019 ( 295 hom. )

Consequence

CHRNB1
NM_000747.3 intron

Scores

Splicing: ADA: 0.00002066

Clinical Significance

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

Conservation

PhyloP100: 0.925

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

congenital myasthenic syndrome 2C
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
congenital myasthenic syndrome 1A
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
congenital myasthenic syndrome 2A
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
postsynaptic congenital myasthenic syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CHRNB1 links:

ENSG00000308645 (HGNC:):

ENSG00000308645 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 17-7454288-C-T is Benign according to our data. Variant chr17-7454288-C-T is described in ClinVar as [Benign]. Clinvar id is 128753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0137 (2088/152276) while in subpopulation NFE AF = 0.0211 (1436/68014). AF 95% confidence interval is 0.0202. There are 26 homozygotes in GnomAd4. There are 963 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 26 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNB1	NM_000747.3 link	c.821-9C>T		intron_variant	Intron 7 of 10	ENST00000306071.7	NP_000738.2	P11230-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB1	ENST00000306071.7 link	c.821-9C>T		intron_variant	Intron 7 of 10	1	NM_000747.3	ENSP00000304290.2		P11230-1

Frequencies

GnomAD3 genomes

AF:

0.0137

AC:

2087

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00372

Gnomad AMI

AF:

0.0473

Gnomad AMR

AF:

0.00851

Gnomad ASJ

AF:

0.0452

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00642

Gnomad FIN

AF:

0.00904

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0211

Gnomad OTH

AF:

0.0172

GnomAD2 exomes

AF:

0.0147

AC:

3684

AN:

251452

AF XY:

0.0150

show subpopulations

Gnomad AFR exome

AF:

0.00246

Gnomad AMR exome

AF:

0.00743

Gnomad ASJ exome

AF:

0.0399

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0111

Gnomad NFE exome

AF:

0.0216

Gnomad OTH exome

AF:

0.0199

GnomAD4 exome

AF:

0.0185

AC:

26935

AN:

1453640

Hom.:

295

Cov.:

AF XY:

0.0184

AC XY:

13324

AN XY:

723748

show subpopulations

African (AFR)

AF:

0.00270

AC:

AN:

33324

American (AMR)

AF:

0.00805

AC:

360

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0412

AC:

1075

AN:

26078

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39666

South Asian (SAS)

AF:

0.00495

AC:

426

AN:

86106

European-Finnish (FIN)

AF:

0.0119

AC:

635

AN:

53392

Middle Eastern (MID)

AF:

0.0113

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0210

AC:

23241

AN:

1104510

Other (OTH)

AF:

0.0173

AC:

1040

AN:

60098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1283

2567

3850

5134

6417

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0137

AC:

2088

AN:

152276

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

963

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00371

AC:

154

AN:

41552

American (AMR)

AF:

0.00850

AC:

130

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0452

AC:

157

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00643

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00904

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0211

AC:

1436

AN:

68014

Other (OTH)

AF:

0.0170

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

108

216

323

431

539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0201

Hom.:

Bravo

AF:

0.0138

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0237

EpiControl

AF:

0.0220

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 27, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

May 18, 2021

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital myasthenic syndrome 2A

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital myasthenic syndrome 4C

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

0.93

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000021

dbscSNV1_RF

Benign

0.014

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs76001008

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over