rs2302765

Positions:

chr17-7447656-T-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000747.3(CHRNB1):c.610+6T>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,613,754 control chromosomes in the GnomAD database, including 21,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2289 hom., cov: 31)

Exomes 𝑓: 0.16 ( 18924 hom. )

Consequence

CHRNB1
NM_000747.3 splice_donor_region, intron

Scores

Splicing: ADA: 0.2278

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.29

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 17-7447656-T-C is Benign according to our data. Variant chr17-7447656-T-C is described in ClinVar as [Benign]. Clinvar id is 128752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7447656-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.205 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.610+6T>C		splice_donor_region_variant, intron_variant		ENST00000306071.7	NP_000738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB1	ENST00000306071.7 linkuse as main transcript	c.610+6T>C		splice_donor_region_variant, intron_variant		1	NM_000747.3	ENSP00000304290	P1	P11230-1

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25216

AN:

151940

Hom.:

2283

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.0999

Gnomad EAS

AF:

0.195

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.152

GnomAD3 exomes

AF:

0.175

AC:

44061

AN:

251400

Hom.:

4164

AF XY:

0.174

AC XY:

23640

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.154

Gnomad AMR exome

AF:

0.206

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.190

Gnomad SAS exome

AF:

0.219

Gnomad FIN exome

AF:

0.244

Gnomad NFE exome

AF:

0.149

Gnomad OTH exome

AF:

0.167

GnomAD4 exome

AF:

0.157

AC:

229039

AN:

1461694

Hom.:

18924

Cov.:

AF XY:

0.158

AC XY:

114756

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.152

Gnomad4 AMR exome

AF:

0.207

Gnomad4 ASJ exome

AF:

0.0997

Gnomad4 EAS exome

AF:

0.201

Gnomad4 SAS exome

AF:

0.216

Gnomad4 FIN exome

AF:

0.239

Gnomad4 NFE exome

AF:

0.146

Gnomad4 OTH exome

AF:

0.159

GnomAD4 genome

AF:

0.166

AC:

25250

AN:

152060

Hom.:

2289

Cov.:

AF XY:

0.172

AC XY:

12778

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.157

Gnomad4 AMR

AF:

0.197

Gnomad4 ASJ

AF:

0.0999

Gnomad4 EAS

AF:

0.195

Gnomad4 SAS

AF:

0.216

Gnomad4 FIN

AF:

0.246

Gnomad4 NFE

AF:

0.151

Gnomad4 OTH

AF:

0.159

Alfa

AF:

0.144

Hom.:

2133

Bravo

AF:

0.160

Asia WGS

AF:

0.270

AC:

936

AN:

3478

EpiCase

AF:

0.131

EpiControl

AF:

0.133

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 19, 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. -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -

Congenital myasthenic syndrome 2A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.23

dbscSNV1_RF

Benign

0.21

SpliceAI score (max)

0.020

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