Variant chr17-7455958-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000306071.7(CHRNB1):c.1365+17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,610,586 control chromosomes in the GnomAD database, including 21,098 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2231 hom., cov: 31)

Exomes 𝑓: 0.16 ( 18867 hom. )

Consequence

CHRNB1
ENST00000306071.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.530

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 17-7455958-T-C is Benign according to our data. Variant chr17-7455958-T-C is described in ClinVar as [Benign]. Clinvar id is 256773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7455958-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.204 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.1365+17T>C		intron_variant		ENST00000306071.7	NP_000738.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
CHRNB1	ENST00000306071.7 linkuse as main transcript	c.1365+17T>C	intron_variant	1	NM_000747.3	ENSP00000304290	P1	P11230-1
CHRNB1	ENST00000536404.6 linkuse as main transcript	c.1149+17T>C	intron_variant	2		ENSP00000439209		P11230-2
CHRNB1	ENST00000575379.1 linkuse as main transcript	c.-28+17T>C	intron_variant	2		ENSP00000461751
CHRNB1	ENST00000576360.1 linkuse as main transcript	c.1002+17T>C	intron_variant	3		ENSP00000459092

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

24960

AN:

149786

Hom.:

2221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.146

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.214

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.0962

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.153

GnomAD3 exomes

AF:

0.175

AC:

43979

AN:

250924

Hom.:

4129

AF XY:

0.174

AC XY:

23570

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.212

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.188

Gnomad SAS exome

AF:

0.217

Gnomad FIN exome

AF:

0.244

Gnomad NFE exome

AF:

0.149

Gnomad OTH exome

AF:

0.167

GnomAD4 exome

AF:

0.156

AC:

228471

AN:

1460716

Hom.:

18867

Cov.:

AF XY:

0.157

AC XY:

114433

AN XY:

726680

show subpopulations

Gnomad4 AFR exome

AF:

0.147

Gnomad4 AMR exome

AF:

0.212

Gnomad4 ASJ exome

AF:

0.0999

Gnomad4 EAS exome

AF:

0.201

Gnomad4 SAS exome

AF:

0.214

Gnomad4 FIN exome

AF:

0.239

Gnomad4 NFE exome

AF:

0.146

Gnomad4 OTH exome

AF:

0.158

GnomAD4 genome

AF:

0.167

AC:

24990

AN:

149870

Hom.:

2231

Cov.:

AF XY:

0.173

AC XY:

12625

AN XY:

73072

show subpopulations

Gnomad4 AFR

AF:

0.157

Gnomad4 AMR

AF:

0.199

Gnomad4 ASJ

AF:

0.101

Gnomad4 EAS

AF:

0.197

Gnomad4 SAS

AF:

0.215

Gnomad4 FIN

AF:

0.253

Gnomad4 NFE

AF:

0.151

Gnomad4 OTH

AF:

0.160

Alfa

AF:

0.142

Hom.:

1625

Bravo

AF:

0.158

Asia WGS

AF:

0.269

AC:

933

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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. -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.7

DANN

Benign

0.50

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

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