rs7210231

chr17-7454545-C-Achr17-7454545-C-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.1044+25C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,587,778 control chromosomes in the GnomAD database, including 35,146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3186 hom., cov: 30)
  • Exomes 𝑓: 0.21 (31960 hom.)
• Consequence: CHRNB1 NM_000747.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.20

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=-0.69).
• BP6: Variant 17-7454545-C-A is Benign according to our data. Variant chr17-7454545-C-A is described in ClinVar as [Benign]. Clinvar id is 256771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNB1	NM_000747.3	c.1044+25C>A		intron_variant		ENST00000306071.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNB1	ENST00000306071.7	c.1044+25C>A		intron_variant		1	NM_000747.3	P1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30186 AN: 151950 Hom.: 3191 Cov.: 30

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.0360

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.211

GnomAD3 exomes AF: 0.192 AC: 48042 AN: 250578 Hom.: 5162 AF XY: 0.200 AC XY: 27078 AN XY: 135462

Gnomad AFR exome AF: 0.220

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.0401

Gnomad SAS exome AF: 0.280

Gnomad FIN exome AF: 0.178

Gnomad NFE exome AF: 0.212

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.206 AC: 295078 AN: 1435710 Hom.: 31960 Cov.: 27 AF XY: 0.208 AC XY: 148654 AN XY: 715810

Gnomad4 AFR exome AF: 0.217

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.228

Gnomad4 EAS exome AF: 0.0529

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.181

Gnomad4 NFE exome AF: 0.209

Gnomad4 OTH exome AF: 0.206

GnomAD4 genome AF: 0.199 AC: 30189 AN: 152068 Hom.: 3186 Cov.: 30 AF XY: 0.196 AC XY: 14584 AN XY: 74340

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.0361

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.208

Alfa AF: 0.162 Hom.: 530

Bravo AF: 0.198

Asia WGS AF: 0.148 AC: 516 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

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	-0.69
Cadd	Benign	6.4
Dann	Benign	0.78

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: rs7210231; hg19: chr17-7357864; COSMIC: COSV60140501; COSMIC: COSV60140501;