rs8042059

Variant names:

• chr15-78615517-A-C
• rs8042059
• NM_000743.5:c.377+1507T>G

Your query was ambiguous. Multiple possible variants found:

• chr15-78615517-A-C
• chr15-78615517-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.377+1507T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 151,988 control chromosomes in the GnomAD database, including 8,037 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 0.30 (8037 hom., cov: 31)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 23 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA3	NM_000743.5	c.377+1507T>G		intron_variant	Intron 4 of 5	ENST00000326828.6	NP_000734.2
CHRNA3	NM_001166694.2	c.377+1507T>G		intron_variant	Intron 4 of 5		NP_001160166.1
CHRNA3	NR_046313.2	n.579+1507T>G		intron_variant	Intron 4 of 7
CHRNA3	XM_006720382.4	c.176+1507T>G		intron_variant	Intron 4 of 5		XP_006720445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA3	ENST00000326828.6	c.377+1507T>G		intron_variant	Intron 4 of 5	1	NM_000743.5	ENSP00000315602.5
CHRNA3	ENST00000348639.7	c.377+1507T>G		intron_variant	Intron 4 of 5	1		ENSP00000267951.4
CHRNA3	ENST00000559658.5	n.377+1507T>G		intron_variant	Intron 4 of 7	2		ENSP00000452896.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45646 AN: 151870 Hom.: 8011 Cov.: 31

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.298

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.301 AC: 45713 AN: 151988 Hom.: 8037 Cov.: 31 AF XY: 0.309 AC XY: 22945 AN XY: 74272

African (AFR) AF: 0.298 AC: 12366 AN: 41434

American (AMR) AF: 0.477 AC: 7282 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 801 AN: 3468

East Asian (EAS) AF: 0.713 AC: 3681 AN: 5166

South Asian (SAS) AF: 0.449 AC: 2163 AN: 4816

European-Finnish (FIN) AF: 0.294 AC: 3101 AN: 10550

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15431 AN: 67956

Other (OTH) AF: 0.305 AC: 645 AN: 2114

Alfa AF: 0.211 Hom.: 737

Bravo AF: 0.316

Asia WGS AF: 0.571 AC: 1984 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.41
PhyloP100		-1.1
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: rs8042059; hg19: chr15-78907859;