rs578776
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000743.5(CHRNA3):c.*546C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 980,552 control chromosomes in the GnomAD database, including 51,406 homozygotes. 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: 𝑓 0.40 ( 13877 hom., cov: 32)
Exomes 𝑓: 0.29 ( 37529 hom. )
Consequence
CHRNA3
NM_000743.5 3_prime_UTR
NM_000743.5 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.269
Genes affected
CHRNA3 (HGNC:1957): (cholinergic receptor nicotinic alpha 3 subunit) This locus encodes a member of the nicotinic acetylcholine receptor family of proteins. Members of this family of proteins form pentameric complexes comprised of both alpha and beta subunits. This locus encodes an alpha-type subunit, as it contains characteristic adjacent cysteine residues. The encoded protein is a ligand-gated ion channel that likely plays a role in neurotransmission. Polymorphisms in this gene have been associated with an increased risk of smoking initiation and an increased susceptibility to lung cancer. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CHRNA3 | NM_000743.5 | c.*546C>T | 3_prime_UTR_variant | Exon 6 of 6 | ENST00000326828.6 | NP_000734.2 | ||
CHRNA3 | XM_006720382.4 | c.*546C>T | 3_prime_UTR_variant | Exon 6 of 6 | XP_006720445.1 | |||
CHRNA3 | NM_001166694.2 | c.1390-2867C>T | intron_variant | Intron 5 of 5 | NP_001160166.1 | |||
CHRNA3 | NR_046313.2 | n.1784+482C>T | intron_variant | Intron 6 of 7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CHRNA3 | ENST00000326828 | c.*546C>T | 3_prime_UTR_variant | Exon 6 of 6 | 1 | NM_000743.5 | ENSP00000315602.5 | |||
CHRNA3 | ENST00000348639.7 | c.1390-2867C>T | intron_variant | Intron 5 of 5 | 1 | ENSP00000267951.4 | ||||
CHRNA3 | ENST00000559002.5 | n.193+482C>T | intron_variant | Intron 1 of 1 | 1 | |||||
CHRNA3 | ENST00000559658.5 | n.*64+482C>T | intron_variant | Intron 6 of 7 | 2 | ENSP00000452896.1 |
Frequencies
GnomAD3 genomes AF: 0.399 AC: 60651AN: 151952Hom.: 13846 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
60651
AN:
151952
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.293 AC: 242706AN: 828482Hom.: 37529 Cov.: 21 AF XY: 0.292 AC XY: 111870AN XY: 382700 show subpopulations
GnomAD4 exome
AF:
AC:
242706
AN:
828482
Hom.:
Cov.:
21
AF XY:
AC XY:
111870
AN XY:
382700
Gnomad4 AFR exome
AF:
AC:
8820
AN:
15646
Gnomad4 AMR exome
AF:
AC:
581
AN:
982
Gnomad4 ASJ exome
AF:
AC:
1315
AN:
5126
Gnomad4 EAS exome
AF:
AC:
2863
AN:
3594
Gnomad4 SAS exome
AF:
AC:
7401
AN:
16352
Gnomad4 FIN exome
AF:
AC:
95
AN:
276
Gnomad4 NFE exome
AF:
AC:
211765
AN:
757790
Gnomad4 Remaining exome
AF:
AC:
9310
AN:
27116
Heterozygous variant carriers
0
7215
14430
21645
28860
36075
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
9824
19648
29472
39296
49120
<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: 0.399 AC: 60734AN: 152070Hom.: 13877 Cov.: 32 AF XY: 0.406 AC XY: 30156AN XY: 74350 show subpopulations
GnomAD4 genome
AF:
AC:
60734
AN:
152070
Hom.:
Cov.:
32
AF XY:
AC XY:
30156
AN XY:
74350
Gnomad4 AFR
AF:
AC:
0.538491
AN:
0.538491
Gnomad4 AMR
AF:
AC:
0.526285
AN:
0.526285
Gnomad4 ASJ
AF:
AC:
0.266724
AN:
0.266724
Gnomad4 EAS
AF:
AC:
0.785466
AN:
0.785466
Gnomad4 SAS
AF:
AC:
0.46932
AN:
0.46932
Gnomad4 FIN
AF:
AC:
0.320726
AN:
0.320726
Gnomad4 NFE
AF:
AC:
0.27401
AN:
0.27401
Gnomad4 OTH
AF:
AC:
0.392148
AN:
0.392148
Heterozygous variant carriers
0
1722
3444
5165
6887
8609
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
556
1112
1668
2224
2780
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
2161
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
Mutation Taster
=100/0
polymorphism (auto)
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at