15-78615314-T-C

Variant names:

• chr15-78615314-T-C
• rs6495308
• NM_000743.5:c.377+1710A>G

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+1710A>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 151,980 control chromosomes in the GnomAD database, including 8,056 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 (8056 hom., cov: 32)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.314
• Publications: 74 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 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.377+1710A>G		intron	N/A	NP_000734.2
	CHRNA3	NM_001166694.2		c.377+1710A>G		intron	N/A	NP_001160166.1
	CHRNA3	NR_046313.2		n.579+1710A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA3	ENST00000326828.6	TSL:1 MANE Select	c.377+1710A>G		intron	N/A	ENSP00000315602.5
	CHRNA3	ENST00000348639.7	TSL:1	c.377+1710A>G		intron	N/A	ENSP00000267951.4
	CHRNA3	ENST00000893003.1		c.509+1710A>G		intron	N/A	ENSP00000563062.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45709 AN: 151862 Hom.: 8030 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.301 AC: 45776 AN: 151980 Hom.: 8056 Cov.: 32 AF XY: 0.309 AC XY: 22990 AN XY: 74304

African (AFR) AF: 0.299 AC: 12385 AN: 41432

American (AMR) AF: 0.478 AC: 7301 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 802 AN: 3464

East Asian (EAS) AF: 0.713 AC: 3686 AN: 5172

South Asian (SAS) AF: 0.449 AC: 2164 AN: 4820

European-Finnish (FIN) AF: 0.295 AC: 3118 AN: 10580

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

European-Non Finnish (NFE) AF: 0.227 AC: 15432 AN: 67918

Other (OTH) AF: 0.307 AC: 645 AN: 2102

Alfa AF: 0.264 Hom.: 18431

Bravo AF: 0.316

Asia WGS AF: 0.571 AC: 1984 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.49
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs6495308; hg19: chr15-78907656;