rs17856697

Positions:

• chr17-7445306-A-C
• chr17-7445306-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000747.3(CHRNB1):​c.95A>C​(p.Glu32Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E32G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHRNB1 NM_000747.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.06

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25599366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNB1	NM_000747.3	c.95A>C	p.Glu32Ala	missense_variant	2/11	ENST00000306071.7	NP_000738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB1	ENST00000306071.7	c.95A>C	p.Glu32Ala	missense_variant	2/11	1	NM_000747.3	ENSP00000304290	P1
CHRNB1	ENST00000572857.5	c.95A>C	p.Glu32Ala	missense_variant	2/6	4		ENSP00000461402
CHRNB1	ENST00000574054.1	n.115A>C		non_coding_transcript_exon_variant	2/2	2
CHRNB1	ENST00000570557.5			upstream_gene_variant		5		ENSP00000460648

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	23
DANN	Benign	0.95
DEOGEN2	Benign	0.28	T;.
Eigen	Benign	0.19
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.3	L;.
MutationTaster	Benign	0.59	N;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.1	N;.
REVEL	Benign	0.28
Sift	Benign	0.65	T;.
Sift4G	Benign	0.53	T;T
Polyphen		0.41	B;.
Vest4		0.22
MutPred		0.33		Gain of MoRF binding (P = 0.0305);Gain of MoRF binding (P = 0.0305);
MVP		0.89
MPC		0.58
ClinPred		0.73	D
GERP RS		5.4
Varity_R		0.15
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17856697; hg19: chr17-7348625;