15-78603787-A-G

Variant names:

• chr15-78603787-A-G
• rs1317286
• NM_000743.5:c.378-1523T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000743.5(CHRNA3):​c.378-1523T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,946 control chromosomes in the GnomAD database, including 7,208 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 (7208 hom., cov: 31)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328
• Publications: 68 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.346 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.378-1523T>C		intron	N/A	NP_000734.2
	CHRNA3	NM_001166694.2		c.378-1523T>C		intron	N/A	NP_001160166.1
	CHRNA3	NR_046313.2		n.580-1523T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA3	ENST00000326828.6	TSL:1 MANE Select	c.378-1523T>C		intron	N/A	ENSP00000315602.5
	CHRNA3	ENST00000348639.7	TSL:1	c.378-1523T>C		intron	N/A	ENSP00000267951.4
	CHRNA3	ENST00000558903.1	TSL:4	n.85-1523T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45371 AN: 151828 Hom.: 7212 Cov.: 31

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.0996

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.299 AC: 45382 AN: 151946 Hom.: 7208 Cov.: 31 AF XY: 0.295 AC XY: 21893 AN XY: 74256

African (AFR) AF: 0.244 AC: 10117 AN: 41452

American (AMR) AF: 0.249 AC: 3804 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1439 AN: 3472

East Asian (EAS) AF: 0.0997 AC: 515 AN: 5168

South Asian (SAS) AF: 0.226 AC: 1084 AN: 4792

European-Finnish (FIN) AF: 0.327 AC: 3452 AN: 10554

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23783 AN: 67924

Other (OTH) AF: 0.324 AC: 682 AN: 2106

Alfa AF: 0.300 Hom.: 4975

Bravo AF: 0.289

Asia WGS AF: 0.150 AC: 527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.3
DANN	Benign	0.81
PhyloP100		-0.33
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: rs1317286; hg19: chr15-78896129;