17-7454281-C-T

Variant names:

• chr17-7454281-C-T
• rs371190837
• NM_000747.3:c.821-16C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000747.3(CHRNB1):​c.821-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000166 in 1,444,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: CHRNB1 NM_000747.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 2C

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp, ClinGen
• congenital myasthenic syndrome 1A

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• congenital myasthenic syndrome 2A

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• postsynaptic congenital myasthenic syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000308645 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000747.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB1	NM_000747.3	MANE Select	c.821-16C>T		intron	N/A	NP_000738.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB1	ENST00000306071.7	TSL:1 MANE Select	c.821-16C>T		intron	N/A	ENSP00000304290.2
	CHRNB1	ENST00000536404.6	TSL:2	c.605-16C>T		intron	N/A	ENSP00000439209.2
	CHRNB1	ENST00000576360.1	TSL:3	c.605-163C>T		intron	N/A	ENSP00000459092.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.0000166 AC: 24 AN: 1444120 Hom.: 0 Cov.: 29 AF XY: 0.0000125 AC XY: 9 AN XY: 719604

African (AFR) AF: 0.00 AC: 0 AN: 33164

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26024

East Asian (EAS) AF: 0.00 AC: 0 AN: 39628

South Asian (SAS) AF: 0.00 AC: 0 AN: 85910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.0000219 AC: 24 AN: 1095826

Other (OTH) AF: 0.00 AC: 0 AN: 59804

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.0
DANN	Benign	0.69
PhyloP100		-0.29

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

Other links and lift over

dbSNP: rs371190837; hg19: chr17-7357600;