rs472054

Variant names:

• chr15-78595652-A-G
• rs472054
• NM_000743.5:c.*952T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 25 publications found

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 Gene-Disease associations (from GenCC):

• urinary bladder, atony of

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CHRNA3	NM_000743.5	c.*952T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000326828.6	NP_000734.2
CHRNA3	XM_006720382.4	c.*952T>C		3_prime_UTR_variant	Exon 6 of 6		XP_006720445.1
CHRNA3	NM_001166694.2	c.1390-2461T>C		intron_variant	Intron 5 of 5		NP_001160166.1
CHRNA3	NR_046313.2	n.1784+888T>C		intron_variant	Intron 6 of 7

Ensembl

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

African (AFR) AF: 0.900 AC: 9 AN: 10

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.833 AC: 5 AN: 6

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 0.667 AC: 4 AN: 6

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.601 AC: 404 AN: 672

Other (OTH) AF: 0.607 AC: 17 AN: 28

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

African (AFR) AF: 0.716 AC: 29663 AN: 41436

American (AMR) AF: 0.768 AC: 11733 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2269 AN: 3470

East Asian (EAS) AF: 0.818 AC: 4243 AN: 5184

South Asian (SAS) AF: 0.701 AC: 3374 AN: 4810

European-Finnish (FIN) AF: 0.650 AC: 6853 AN: 10550

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42773 AN: 67944

Other (OTH) AF: 0.698 AC: 1470 AN: 2106

Alfa AF: 0.648 Hom.: 83797

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
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs472054; hg19: chr15-78887994;