NM_000747.3:c.44C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000747.3(CHRNB1):c.44C>T(p.Ala15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000441 in 1,609,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A15G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

CHRNB1
NM_000747.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.387

Publications

2 publications found

Variant links:

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 links:

ENSG00000272884 (HGNC:):

ENSG00000272884 links:

FGF11 (HGNC:3667): (fibroblast growth factor 11) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. The function of this gene has not yet been determined. The expression pattern of the mouse homolog implies a role in nervous system development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

FGF11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.078247845).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHRNB1	NM_000747.3	MANE Select	c.44C>T	p.Ala15Val	missense	Exon 1 of 11	NP_000738.2
FGF11	NM_004112.4	MANE Select	c.*2025C>T		downstream_gene	N/A	NP_004103.1	Q92914
FGF11	NM_001303460.2		c.*2025C>T		downstream_gene	N/A	NP_001290389.1	B7Z1C3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHRNB1	ENST00000306071.7	TSL:1 MANE Select	c.44C>T	p.Ala15Val	missense	Exon 1 of 11	ENSP00000304290.2	P11230-1
ENSG00000272884	ENST00000575331.1	TSL:1	n.4758C>T		non_coding_transcript_exon	Exon 3 of 3
CHRNB1	ENST00000572857.5	TSL:4	c.44C>T	p.Ala15Val	missense	Exon 1 of 6	ENSP00000461402.1	I3L4N5

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000172

AC:

AN:

233154

AF XY:

0.0000311

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000389

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000480

AC:

AN:

1457026

Hom.:

Cov.:

AF XY:

0.0000511

AC XY:

AN XY:

724742

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33436

American (AMR)

AF:

0.00

AC:

AN:

44578

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26066

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39660

South Asian (SAS)

AF:

0.00

AC:

AN:

86074

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5266

European-Non Finnish (NFE)

AF:

0.0000621

AC:

AN:

1111240

Other (OTH)

AF:

0.00

AC:

AN:

60148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152064

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41410

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67990

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000831

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Congenital myasthenic syndrome 2A (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.056

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.041

M_CAP

Benign

0.015

MetaRNN

Benign

0.078

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.35

PhyloP100

-0.39

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.20

REVEL

Benign

0.19

Sift

Benign

0.30

Sift4G

Benign

0.65

Polyphen

0.0010

Vest4

0.098

MutPred

0.35

Loss of disorder (P = 0.0432)

MVP

0.64

MPC

0.40

ClinPred

0.12

GERP RS

-1.0

PromoterAI

-0.025

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.029

gMVP

0.42

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over