rs615470

Positions:

• chr15-78593646-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000745.4(CHRNA5):​c.*393T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 156,536 control chromosomes in the GnomAD database, including 32,830 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 0.64 (31870 hom., cov: 33)
  • Exomes 𝑓: 0.66 (960 hom.)
• Consequence: CHRNA5 NM_000745.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.527

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]

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]

CHRNA3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.*393T>C		3_prime_UTR_variant	6/6	ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9	c.*393T>C		3_prime_UTR_variant	6/6	1	NM_000745.4	ENSP00000299565.5

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97904 AN: 151946 Hom.: 31834 Cov.: 33

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.669

GnomAD4 exome AF: 0.659 AC: 2948 AN: 4474 Hom.: 960 Cov.: 0 AF XY: 0.657 AC XY: 1567 AN XY: 2386

Gnomad4 AFR exome AF: 0.566

Gnomad4 AMR exome AF: 0.772

Gnomad4 ASJ exome AF: 0.675

Gnomad4 EAS exome AF: 0.845

Gnomad4 SAS exome AF: 0.689

Gnomad4 FIN exome AF: 0.679

Gnomad4 NFE exome AF: 0.635

Gnomad4 OTH exome AF: 0.629

GnomAD4 genome AF: 0.644 AC: 97989 AN: 152062 Hom.: 31870 Cov.: 33 AF XY: 0.647 AC XY: 48101 AN XY: 74306

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.757

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.699

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.673

Alfa AF: 0.643 Hom.: 30674

Bravo AF: 0.650

Asia WGS AF: 0.743 AC: 2584 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.9
DANN	Benign	0.90

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

Other links and lift over

dbSNP: rs615470; hg19: chr15-78885988;