rs12452047

Positions:

• chr17-7448517-A-G

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.611-62A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,539,548 control chromosomes in the GnomAD database, including 20,402 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2347 hom., cov: 31)
  • Exomes 𝑓: 0.16 (18055 hom.)
• Consequence: CHRNB1 NM_000747.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.162

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 17-7448517-A-G is Benign according to our data. Variant chr17-7448517-A-G is described in ClinVar as [Benign]. Clinvar id is 1262506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7448517-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNB1	NM_000747.3	c.611-62A>G		intron_variant		ENST00000306071.7	NP_000738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB1	ENST00000306071.7	c.611-62A>G		intron_variant		1	NM_000747.3	ENSP00000304290.2

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25612 AN: 152062 Hom.: 2340 Cov.: 31

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.153

GnomAD4 exome AF: 0.158 AC: 218672 AN: 1387366 Hom.: 18055 AF XY: 0.159 AC XY: 109968 AN XY: 693214

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.207

Gnomad4 ASJ exome AF: 0.100

Gnomad4 EAS exome AF: 0.201

Gnomad4 SAS exome AF: 0.216

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.147

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.169 AC: 25650 AN: 152182 Hom.: 2347 Cov.: 31 AF XY: 0.174 AC XY: 12962 AN XY: 74396

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.160

Alfa AF: 0.146 Hom.: 1677

Bravo AF: 0.162

Asia WGS AF: 0.270 AC: 936 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	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.8
DANN	Benign	0.84

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: rs12452047; hg19: chr17-7351836;