rs481134

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000745.4(CHRNA5):​c.259-1424A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 151,986 control chromosomes in the GnomAD database, including 32,195 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 0.65 ( 32195 hom., cov: 32)

Consequence

CHRNA5
NM_000745.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.53
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CHRNA5NM_000745.4 linkc.259-1424A>G intron_variant ENST00000299565.9 NP_000736.2 P30532Q6EWN4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CHRNA5ENST00000299565.9 linkc.259-1424A>G intron_variant 1 NM_000745.4 ENSP00000299565.5 P30532
CHRNA5ENST00000394802.4 linkc.73-1424A>G intron_variant 3 ENSP00000378281.4 H7BYM0
CHRNA5ENST00000559554.5 linkc.259-1424A>G intron_variant 3 ENSP00000453519.1 H0YM98

Frequencies

GnomAD3 genomes
AF:
0.646
AC:
98100
AN:
151866
Hom.:
32143
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.703
Gnomad AMI
AF:
0.567
Gnomad AMR
AF:
0.745
Gnomad ASJ
AF:
0.637
Gnomad EAS
AF:
0.820
Gnomad SAS
AF:
0.670
Gnomad FIN
AF:
0.626
Gnomad MID
AF:
0.782
Gnomad NFE
AF:
0.577
Gnomad OTH
AF:
0.670
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.646
AC:
98214
AN:
151986
Hom.:
32195
Cov.:
32
AF XY:
0.651
AC XY:
48345
AN XY:
74288
show subpopulations
Gnomad4 AFR
AF:
0.703
Gnomad4 AMR
AF:
0.746
Gnomad4 ASJ
AF:
0.637
Gnomad4 EAS
AF:
0.821
Gnomad4 SAS
AF:
0.671
Gnomad4 FIN
AF:
0.626
Gnomad4 NFE
AF:
0.577
Gnomad4 OTH
AF:
0.674
Alfa
AF:
0.652
Hom.:
7736
Bravo
AF:
0.658
Asia WGS
AF:
0.735
AC:
2558
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.22
DANN
Benign
0.79

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: rs481134; hg19: chr15-78877563; API