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GeneBe

15-78580878-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_000745.4(CHRNA5):c.174C>T(p.Tyr58=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00308 in 1,613,482 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 56 hom., cov: 33)
Exomes 𝑓: 0.0017 ( 62 hom. )

Consequence

CHRNA5
NM_000745.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.416
Variant links:
Genes affected
CHRNA5 (HGNC:1959): (cholinergic receptor nicotinic alpha 5 subunit) The protein encoded by this gene is a nicotinic acetylcholine receptor subunit and a member of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. These receptors are thought to be heteropentamers composed of separate but similar subunits. Defects in this gene have been linked to susceptibility to lung cancer type 2 (LNCR2).[provided by RefSeq, Jun 2010]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-78580878-C-T is Benign according to our data. Variant chr15-78580878-C-T is described in ClinVar as [Benign]. Clinvar id is 714660.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.416 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.053 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CHRNA5NM_000745.4 linkuse as main transcriptc.174C>T p.Tyr58= synonymous_variant 2/6 ENST00000299565.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CHRNA5ENST00000299565.9 linkuse as main transcriptc.174C>T p.Tyr58= synonymous_variant 2/61 NM_000745.4 P1
CHRNA5ENST00000559554.5 linkuse as main transcriptc.174C>T p.Tyr58= synonymous_variant 2/63
CHRNA5ENST00000394802.4 linkuse as main transcript upstream_gene_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0158
AC:
2411
AN:
152184
Hom.:
56
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0547
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00504
Gnomad ASJ
AF:
0.00520
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000338
Gnomad OTH
AF:
0.0110
GnomAD3 exomes
AF:
0.00418
AC:
1052
AN:
251408
Hom.:
25
AF XY:
0.00301
AC XY:
409
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.0541
Gnomad AMR exome
AF:
0.00220
Gnomad ASJ exome
AF:
0.00516
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000273
Gnomad OTH exome
AF:
0.00212
GnomAD4 exome
AF:
0.00175
AC:
2555
AN:
1461180
Hom.:
62
Cov.:
30
AF XY:
0.00154
AC XY:
1118
AN XY:
726964
show subpopulations
Gnomad4 AFR exome
AF:
0.0565
Gnomad4 AMR exome
AF:
0.00268
Gnomad4 ASJ exome
AF:
0.00555
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000162
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000130
Gnomad4 OTH exome
AF:
0.00373
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0159
AC:
2422
AN:
152302
Hom.:
56
Cov.:
33
AF XY:
0.0152
AC XY:
1132
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.0548
Gnomad4 AMR
AF:
0.00497
Gnomad4 ASJ
AF:
0.00520
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000338
Gnomad4 OTH
AF:
0.0109
Alfa
AF:
0.0612
Hom.:
2363
Bravo
AF:
0.0177
Asia WGS
AF:
0.00491
AC:
17
AN:
3478
EpiCase
AF:
0.000436
EpiControl
AF:
0.000415

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
Cadd
Benign
4.7
Dann
Benign
0.60

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: rs79835149; hg19: chr15-78873220; API