rs578776

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.269
Variant links:
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]

Genome browser will be placed here

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
CHRNA3NM_000743.5 linkc.*546C>T 3_prime_UTR_variant Exon 6 of 6 ENST00000326828.6 NP_000734.2 P32297-2
CHRNA3XM_006720382.4 linkc.*546C>T 3_prime_UTR_variant Exon 6 of 6 XP_006720445.1
CHRNA3NM_001166694.2 linkc.1390-2867C>T intron_variant Intron 5 of 5 NP_001160166.1 P32297-3
CHRNA3NR_046313.2 linkn.1784+482C>T intron_variant Intron 6 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHRNA3ENST00000326828 linkc.*546C>T 3_prime_UTR_variant Exon 6 of 6 1 NM_000743.5 ENSP00000315602.5 P32297-2
CHRNA3ENST00000348639.7 linkc.1390-2867C>T intron_variant Intron 5 of 5 1 ENSP00000267951.4 P32297-3
CHRNA3ENST00000559002.5 linkn.193+482C>T intron_variant Intron 1 of 1 1
CHRNA3ENST00000559658.5 linkn.*64+482C>T intron_variant Intron 6 of 7 2 ENSP00000452896.1 P32297-2

Frequencies

GnomAD3 genomes
AF:
0.399
AC:
60651
AN:
151952
Hom.:
13846
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.539
Gnomad AMI
AF:
0.169
Gnomad AMR
AF:
0.525
Gnomad ASJ
AF:
0.267
Gnomad EAS
AF:
0.785
Gnomad SAS
AF:
0.470
Gnomad FIN
AF:
0.321
Gnomad MID
AF:
0.380
Gnomad NFE
AF:
0.274
Gnomad OTH
AF:
0.386
GnomAD4 exome
AF:
0.293
AC:
242706
AN:
828482
Hom.:
37529
Cov.:
21
AF XY:
0.292
AC XY:
111870
AN XY:
382700
show subpopulations
Gnomad4 AFR exome
AF:
0.564
AC:
8820
AN:
15646
Gnomad4 AMR exome
AF:
0.592
AC:
581
AN:
982
Gnomad4 ASJ exome
AF:
0.257
AC:
1315
AN:
5126
Gnomad4 EAS exome
AF:
0.797
AC:
2863
AN:
3594
Gnomad4 SAS exome
AF:
0.453
AC:
7401
AN:
16352
Gnomad4 FIN exome
AF:
0.344
AC:
95
AN:
276
Gnomad4 NFE exome
AF:
0.279
AC:
211765
AN:
757790
Gnomad4 Remaining exome
AF:
0.343
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:
60734
AN:
152070
Hom.:
13877
Cov.:
32
AF XY:
0.406
AC XY:
30156
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.538
AC:
0.538491
AN:
0.538491
Gnomad4 AMR
AF:
0.526
AC:
0.526285
AN:
0.526285
Gnomad4 ASJ
AF:
0.267
AC:
0.266724
AN:
0.266724
Gnomad4 EAS
AF:
0.785
AC:
0.785466
AN:
0.785466
Gnomad4 SAS
AF:
0.469
AC:
0.46932
AN:
0.46932
Gnomad4 FIN
AF:
0.321
AC:
0.320726
AN:
0.320726
Gnomad4 NFE
AF:
0.274
AC:
0.27401
AN:
0.27401
Gnomad4 OTH
AF:
0.392
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:
0.324
Hom.:
41970
Bravo
AF:
0.422
Asia WGS
AF:
0.622
AC:
2161
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.66
DANN
Benign
0.53
Mutation Taster
=100/0
polymorphism (auto)

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs578776; hg19: chr15-78888400; API