17-7455958-T-C

Variant summary

Our verdict is Benign. Variant got -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:3
• Conservation: PhyloP100: -0.530

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]

ACMG classification

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	UniProt
CHRNB1	NM_000747.3	c.1365+17T>C		intron_variant		ENST00000306071.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNB1	ENST00000306071.7	c.1365+17T>C		intron_variant		1	NM_000747.3	P1
CHRNB1	ENST00000536404.6	c.1149+17T>C		intron_variant		2
CHRNB1	ENST00000575379.1	c.-28+17T>C		intron_variant		2
CHRNB1	ENST00000576360.1	c.1002+17T>C		intron_variant		3

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

GnomAD3 exomes AF: 0.175 AC: 43979 AN: 250924 Hom.: 4129 AF XY: 0.174 AC XY: 23570 AN XY: 135714

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

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.: 31 AF XY: 0.173 AC XY: 12625 AN XY: 73072

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:3

Revision: criteria provided, multiple submitters, no conflicts

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

Invitae

Jan 31, 2024

- -

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

Other links and lift over

dbSNP: rs2302763; hg19: chr17-7359277; COSMIC: COSV60139438; COSMIC: COSV60139438;