rs4796418

Variant names:

• chr17-7454681-C-G
• rs4796418
• NM_000747.3:c.1044+161C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000747.3(CHRNB1):​c.1044+161C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 151,912 control chromosomes in the GnomAD database, including 2,207 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2207 hom., cov: 30)
• Consequence: CHRNB1 NM_000747.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.383
• Publications: 8 publications found

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

ENSG00000308645 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-7454681-C-G is Benign according to our data. Variant chr17-7454681-C-G is described in ClinVar as Benign. ClinVar VariationId is 1178540.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNB1	NM_000747.3	c.1044+161C>G		intron_variant	Intron 8 of 10	ENST00000306071.7	NP_000738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB1	ENST00000306071.7	c.1044+161C>G		intron_variant	Intron 8 of 10	1	NM_000747.3	ENSP00000304290.2

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24780 AN: 151794 Hom.: 2197 Cov.: 30

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.152

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.163 AC: 24809 AN: 151912 Hom.: 2207 Cov.: 30 AF XY: 0.169 AC XY: 12556 AN XY: 74218

African (AFR) AF: 0.148 AC: 6118 AN: 41404

American (AMR) AF: 0.196 AC: 2997 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 347 AN: 3468

East Asian (EAS) AF: 0.194 AC: 1005 AN: 5176

South Asian (SAS) AF: 0.214 AC: 1027 AN: 4806

European-Finnish (FIN) AF: 0.247 AC: 2593 AN: 10502

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10226 AN: 67984

Other (OTH) AF: 0.159 AC: 337 AN: 2114

Alfa AF: 0.170 Hom.: 271

Bravo AF: 0.157

Asia WGS AF: 0.269 AC: 933 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.36
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4796418; hg19: chr17-7358000;