rs75926342

Variant names:

• chr17-7445171-C-A
• rs75926342
• NM_000747.3:c.44C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-7445171-C-A
• chr17-7445171-C-G
• chr17-7445171-C-T

Variant summary

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

The NM_000747.3(CHRNB1):​c.44C>A​(p.Ala15Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHRNB1 NM_000747.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387

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]

ENSG00000272884 (HGNC:):

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=0.15768269).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNB1	NM_000747.3	c.44C>A	p.Ala15Glu	missense_variant	Exon 1 of 11	ENST00000306071.7	NP_000738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB1	ENST00000306071.7	c.44C>A	p.Ala15Glu	missense_variant	Exon 1 of 11	1	NM_000747.3	ENSP00000304290.2
ENSG00000272884	ENST00000575331.1	n.4758C>A		non_coding_transcript_exon_variant	Exon 3 of 3	1
CHRNB1	ENST00000572857.5	c.44C>A	p.Ala15Glu	missense_variant	Exon 1 of 6	4		ENSP00000461402.1
CHRNB1	ENST00000574054.1	n.64C>A		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1457028 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724744

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.14	T;.
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.22	N
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.5	N;.
REVEL	Uncertain	0.41
Sift	Benign	0.10	T;.
Sift4G	Benign	0.34	T;D
Polyphen		0.18	B;.
Vest4		0.38
MutPred		0.36		Gain of disorder (P = 0.0449);Gain of disorder (P = 0.0449);
MVP		0.74
MPC		0.47
ClinPred		0.33	T
GERP RS		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.11
gMVP		0.53

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: rs75926342; hg19: chr17-7348490;