15-78604205-G-A

Variant names:

• chr15-78604205-G-A
• rs938682
• NM_000743.5:c.378-1941C>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.378-1941C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 152,096 control chromosomes in the GnomAD database, including 39,306 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 0.71 (39306 hom., cov: 32)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336
• Publications: 62 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000743.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA3	NM_000743.5	MANE Select	c.378-1941C>T		intron	N/A	NP_000734.2
	CHRNA3	NM_001166694.2		c.378-1941C>T		intron	N/A	NP_001160166.1
	CHRNA3	NR_046313.2		n.580-1941C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA3	ENST00000326828.6	TSL:1 MANE Select	c.378-1941C>T		intron	N/A	ENSP00000315602.5
	CHRNA3	ENST00000348639.7	TSL:1	c.378-1941C>T		intron	N/A	ENSP00000267951.4
	CHRNA3	ENST00000558903.1	TSL:4	n.85-1941C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108169 AN: 151978 Hom.: 39280 Cov.: 32

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.712 AC: 108228 AN: 152096 Hom.: 39306 Cov.: 32 AF XY: 0.704 AC XY: 52348 AN XY: 74354

African (AFR) AF: 0.713 AC: 29572 AN: 41468

American (AMR) AF: 0.523 AC: 7989 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 2721 AN: 3472

East Asian (EAS) AF: 0.538 AC: 2784 AN: 5174

South Asian (SAS) AF: 0.559 AC: 2696 AN: 4824

European-Finnish (FIN) AF: 0.703 AC: 7451 AN: 10592

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.774 AC: 52577 AN: 67970

Other (OTH) AF: 0.699 AC: 1477 AN: 2114

Alfa AF: 0.740 Hom.: 98843

Bravo AF: 0.698

Asia WGS AF: 0.518 AC: 1806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.6
DANN	Benign	0.46
PhyloP100		0.34
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: rs938682; hg19: chr15-78896547;