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GeneBe

15-78590384-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_000745.4(CHRNA5):c.993C>T(p.Thr331=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,614,090 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 32 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 28 hom. )

Consequence

CHRNA5
NM_000745.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.64
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 -15 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=-0.75).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-78590384-C-T is Benign according to our data. Variant chr15-78590384-C-T is described in ClinVar as [Benign]. Clinvar id is 710275.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=-2.64 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1736/152220) while in subpopulation AFR AF= 0.0382 (1588/41528). AF 95% confidence interval is 0.0367. There are 32 homozygotes in gnomad4. There are 802 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 32 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CHRNA5NM_000745.4 linkuse as main transcriptc.993C>T p.Thr331= synonymous_variant 5/6 ENST00000299565.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CHRNA5ENST00000299565.9 linkuse as main transcriptc.993C>T p.Thr331= synonymous_variant 5/61 NM_000745.4 P1
ENST00000567141.1 linkuse as main transcriptn.893G>A non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0114
AC:
1733
AN:
152102
Hom.:
32
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0383
Gnomad AMI
AF:
0.00987
Gnomad AMR
AF:
0.00609
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000397
Gnomad OTH
AF:
0.00860
GnomAD3 exomes
AF:
0.00317
AC:
796
AN:
251344
Hom.:
12
AF XY:
0.00229
AC XY:
311
AN XY:
135838
show subpopulations
Gnomad AFR exome
AF:
0.0389
Gnomad AMR exome
AF:
0.00254
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000510
Gnomad OTH exome
AF:
0.00212
GnomAD4 exome
AF:
0.00132
AC:
1931
AN:
1461870
Hom.:
28
Cov.:
31
AF XY:
0.00115
AC XY:
837
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.0390
Gnomad4 AMR exome
AF:
0.00349
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000139
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000186
Gnomad4 OTH exome
AF:
0.00349
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0114
AC:
1736
AN:
152220
Hom.:
32
Cov.:
32
AF XY:
0.0108
AC XY:
802
AN XY:
74406
show subpopulations
Gnomad4 AFR
AF:
0.0382
Gnomad4 AMR
AF:
0.00608
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000397
Gnomad4 OTH
AF:
0.00851
Alfa
AF:
0.00207
Hom.:
7
Bravo
AF:
0.0132
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.000654
EpiControl
AF:
0.000593

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
-0.75
Cadd
Benign
0.064
Dann
Benign
0.87

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs61740655; hg19: chr15-78882726; API