rs2302761

Positions:

• chr17-7455201-C-T

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.1045-83C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,470,170 control chromosomes in the GnomAD database, including 31,738 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2692 hom., cov: 30)
  • Exomes 𝑓: 0.20 (29046 hom.)
• Consequence: CHRNB1 NM_000747.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.101

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=-0.71).
• BP6: Variant 17-7455201-C-T is Benign according to our data. Variant chr17-7455201-C-T is described in ClinVar as [Benign]. Clinvar id is 1293280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNB1	NM_000747.3	c.1045-83C>T		intron_variant		ENST00000306071.7	NP_000738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB1	ENST00000306071.7	c.1045-83C>T		intron_variant		1	NM_000747.3	ENSP00000304290	P1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27591 AN: 151910 Hom.: 2697 Cov.: 30

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.0357

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.201

GnomAD4 exome AF: 0.204 AC: 268521 AN: 1318142 Hom.: 29046 AF XY: 0.206 AC XY: 136928 AN XY: 663372

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.228

Gnomad4 EAS exome AF: 0.0528

Gnomad4 SAS exome AF: 0.274

Gnomad4 FIN exome AF: 0.180

Gnomad4 NFE exome AF: 0.210

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.182 AC: 27595 AN: 152028 Hom.: 2692 Cov.: 30 AF XY: 0.180 AC XY: 13355 AN XY: 74304

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.0357

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.199

Alfa AF: 0.206 Hom.: 4747

Bravo AF: 0.179

Asia WGS AF: 0.144 AC: 504 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2302761; hg19: chr17-7358520;