rs472054

Positions:

• chr15-78595652-A-G
• chr15-78595652-A-T

Variant summary

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

The NM_000743.5(CHRNA3):​c.*952T>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 0.678 in 152,708 control chromosomes in the GnomAD database, including 35,427 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 0.68 (35287 hom., cov: 31)
  • Exomes 𝑓: 0.61 (140 hom.)
• Consequence: CHRNA3 NM_000743.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29

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]

CHRNA3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA3	NM_000743.5	c.*952T>C		3_prime_UTR_variant	6/6	ENST00000326828.6	NP_000734.2
CHRNA3	XM_006720382.4	c.*952T>C		3_prime_UTR_variant	6/6		XP_006720445.1
CHRNA3	NM_001166694.2	c.1390-2461T>C		intron_variant			NP_001160166.1
CHRNA3	NR_046313.2	n.1784+888T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA3	ENST00000326828	c.*952T>C		3_prime_UTR_variant	6/6	1	NM_000743.5	ENSP00000315602.5
CHRNA3	ENST00000348639.7	c.1390-2461T>C		intron_variant		1		ENSP00000267951.4
CHRNA3	ENST00000559002.5	n.193+888T>C		intron_variant		1
CHRNA3	ENST00000559658.5	n.*64+888T>C		intron_variant		2		ENSP00000452896.1

Frequencies

GnomAD3 genomes AF: 0.678 AC: 103033 AN: 151864 Hom.: 35243 Cov.: 31

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.694

GnomAD4 exome AF: 0.609 AC: 442 AN: 726 Hom.: 140 Cov.: 3 AF XY: 0.630 AC XY: 237 AN XY: 376

Gnomad4 AFR exome AF: 0.900

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.833

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.667

Gnomad4 NFE exome AF: 0.601

Gnomad4 OTH exome AF: 0.607

GnomAD4 genome AF: 0.679 AC: 103137 AN: 151982 Hom.: 35287 Cov.: 31 AF XY: 0.682 AC XY: 50617 AN XY: 74258

Gnomad4 AFR AF: 0.716

Gnomad4 AMR AF: 0.768

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.818

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.698

Alfa AF: 0.645 Hom.: 47962

Bravo AF: 0.689

Asia WGS AF: 0.755 AC: 2625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.066
DANN	Benign	0.56

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: rs472054; hg19: chr15-78887994;