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GeneBe

rs578776

Variant summary

Our verdict is Benign. Variant got -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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons MANE UniProt
CHRNA3NM_000743.5 linkuse as main transcriptc.*546C>T 3_prime_UTR_variant 6/6 ENST00000326828.6
CHRNA3XM_006720382.4 linkuse as main transcriptc.*546C>T 3_prime_UTR_variant 6/6
CHRNA3NM_001166694.2 linkuse as main transcriptc.1390-2867C>T intron_variant
CHRNA3NR_046313.2 linkuse as main transcriptn.1784+482C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CHRNA3ENST00000326828.6 linkuse as main transcriptc.*546C>T 3_prime_UTR_variant 6/61 NM_000743.5 P1P32297-2
CHRNA3ENST00000348639.7 linkuse as main transcriptc.1390-2867C>T intron_variant 1 P32297-3
CHRNA3ENST00000559002.5 linkuse as main transcriptn.193+482C>T intron_variant, non_coding_transcript_variant 1
CHRNA3ENST00000559658.5 linkuse as main transcriptc.*64+482C>T intron_variant, NMD_transcript_variant 2 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
Gnomad4 AMR exome
AF:
0.592
Gnomad4 ASJ exome
AF:
0.257
Gnomad4 EAS exome
AF:
0.797
Gnomad4 SAS exome
AF:
0.453
Gnomad4 FIN exome
AF:
0.344
Gnomad4 NFE exome
AF:
0.279
Gnomad4 OTH exome
AF:
0.343
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
Gnomad4 AMR
AF:
0.526
Gnomad4 ASJ
AF:
0.267
Gnomad4 EAS
AF:
0.785
Gnomad4 SAS
AF:
0.469
Gnomad4 FIN
AF:
0.321
Gnomad4 NFE
AF:
0.274
Gnomad4 OTH
AF:
0.392
Alfa
AF:
0.306
Hom.:
17525
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

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