NM_000747.3:c.1217+86T>C

Variant names:

• chr17-7455542-T-C
• rs2302762
• NM_000747.3:c.1217+86T>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.1217+86T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 1,527,408 control chromosomes in the GnomAD database, including 364,322 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (29290 hom., cov: 32)
  • Exomes 𝑓: 0.69 (335032 hom.)
• Consequence: CHRNB1 NM_000747.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0870

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=-0.96).
• BP6: Variant 17-7455542-T-C is Benign according to our data. Variant chr17-7455542-T-C is described in ClinVar as [Benign]. Clinvar id is 679143.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNB1	NM_000747.3	c.1217+86T>C		intron_variant	Intron 9 of 10	ENST00000306071.7	NP_000738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB1	ENST00000306071.7	c.1217+86T>C		intron_variant	Intron 9 of 10	1	NM_000747.3	ENSP00000304290.2

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91496 AN: 151914 Hom.: 29290 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.645

GnomAD4 exome AF: 0.690 AC: 948653 AN: 1375376 Hom.: 335032 Cov.: 21 AF XY: 0.689 AC XY: 474074 AN XY: 688348

Gnomad4 AFR exome AF: 0.398

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.679

Gnomad4 EAS exome AF: 0.255

Gnomad4 SAS exome AF: 0.615

Gnomad4 FIN exome AF: 0.700

Gnomad4 NFE exome AF: 0.730

Gnomad4 OTH exome AF: 0.664

GnomAD4 genome AF: 0.602 AC: 91514 AN: 152032 Hom.: 29290 Cov.: 32 AF XY: 0.598 AC XY: 44415 AN XY: 74296

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.610

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.723

Gnomad4 OTH AF: 0.647

Alfa AF: 0.674 Hom.: 24456

Bravo AF: 0.583

Asia WGS AF: 0.472 AC: 1642 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 16, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	8.4
DANN	Benign	0.69

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: rs2302762; hg19: chr17-7358861; COSMIC: COSV60142490; COSMIC: COSV60142490;