rs77592498

Variant names:

• chr17-7447604-C-G
• rs77592498
• NM_000747.3:c.564C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-7447604-C-G
• chr17-7447604-C-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.564C>G​(p.Asp188Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D188D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CHRNB1 NM_000747.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.09
• 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, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
• congenital myasthenic syndrome 1A

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

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.061169624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNB1	NM_000747.3	c.564C>G	p.Asp188Glu	missense_variant	Exon 6 of 11	ENST00000306071.7	NP_000738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB1	ENST00000306071.7	c.564C>G	p.Asp188Glu	missense_variant	Exon 6 of 11	1	NM_000747.3	ENSP00000304290.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461872 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.050
DANN	Benign	0.92
DEOGEN2	Benign	0.16	T;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.033	N
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.061	T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.44	N;.;.
PhyloP100		-3.1
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.2	N;N;.
REVEL	Benign	0.17
Sift	Benign	0.37	T;T;.
Sift4G	Benign	0.24	T;T;T
Polyphen		0.0040	B;.;.
Vest4		0.053
MutPred		0.28		Gain of loop (P = 0.2045);.;.;
MVP		0.48
MPC		0.39
ClinPred		0.050	T
GERP RS		-8.1
Varity_R		0.035
gMVP		0.20
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs77592498; hg19: chr17-7350923;