NM_000747.3:c.1365+17T>C

Variant names:

• chr17-7455958-T-C
• rs2302763
• NM_000747.3:c.1365+17T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000747.3(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 NM_000747.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.530
• Publications: 13 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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 256773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000747.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB1	NM_000747.3	MANE Select	c.1365+17T>C		intron	N/A	NP_000738.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB1	ENST00000306071.7	TSL:1 MANE Select	c.1365+17T>C		intron	N/A	ENSP00000304290.2
	CHRNB1	ENST00000536404.6	TSL:2	c.1149+17T>C		intron	N/A	ENSP00000439209.2
	CHRNB1	ENST00000576360.1	TSL:3	c.1002+17T>C		intron	N/A	ENSP00000459092.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 24960 AN: 149786 Hom.: 2221 Cov.: 31

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

GnomAD2 exomes AF: 0.175 AC: 43979 AN: 250924 AF XY: 0.174

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 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.: 34 AF XY: 0.157 AC XY: 114433 AN XY: 726680

African (AFR) AF: 0.147 AC: 4914 AN: 33420

American (AMR) AF: 0.212 AC: 9481 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.0999 AC: 2609 AN: 26104

East Asian (EAS) AF: 0.201 AC: 7950 AN: 39622

South Asian (SAS) AF: 0.214 AC: 18431 AN: 86230

European-Finnish (FIN) AF: 0.239 AC: 12737 AN: 53342

Middle Eastern (MID) AF: 0.0810 AC: 467 AN: 5764

European-Non Finnish (NFE) AF: 0.146 AC: 162320 AN: 1111232

Other (OTH) AF: 0.158 AC: 9562 AN: 60344

GnomAD4 genome AF: 0.167 AC: 24990 AN: 149870 Hom.: 2231 Cov.: 31 AF XY: 0.173 AC XY: 12625 AN XY: 73072

African (AFR) AF: 0.157 AC: 6340 AN: 40356

American (AMR) AF: 0.199 AC: 2997 AN: 15058

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 347 AN: 3452

East Asian (EAS) AF: 0.197 AC: 998 AN: 5062

South Asian (SAS) AF: 0.215 AC: 1023 AN: 4756

European-Finnish (FIN) AF: 0.253 AC: 2565 AN: 10152

Middle Eastern (MID) AF: 0.0931 AC: 27 AN: 290

European-Non Finnish (NFE) AF: 0.151 AC: 10225 AN: 67744

Other (OTH) AF: 0.160 AC: 336 AN: 2098

Alfa AF: 0.143 Hom.: 1944

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

Submissions by phenotype

not specified Benign:2

Feb 19, 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.

PreventionGenetics, part of Exact Sciences

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

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.7
DANN	Benign	0.50
PhyloP100		-0.53
PromoterAI		0.0091	Neutral
Mutation Taster		=99/1	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: rs2302763; hg19: chr17-7359277; COSMIC: COSV60139438; COSMIC: COSV60139438;