rs3743077

Variant names:

• chr15-78602554-C-T
• rs3743077
• NM_000743.5:c.378-290G>A

Variant summary

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

The NM_000743.5(CHRNA3):​c.378-290G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,080 control chromosomes in the GnomAD database, including 8,500 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 0.31 (8500 hom., cov: 32)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106
• Publications: 35 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 = 0.417 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA3	NM_000743.5	MANE Select	c.378-290G>A		intron	N/A	NP_000734.2
	CHRNA3	NM_001166694.2		c.378-290G>A		intron	N/A	NP_001160166.1	P32297-3
	CHRNA3	NR_046313.2		n.580-290G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA3	ENST00000326828.6	TSL:1 MANE Select	c.378-290G>A		intron	N/A	ENSP00000315602.5	P32297-2
	CHRNA3	ENST00000348639.7	TSL:1	c.378-290G>A		intron	N/A	ENSP00000267951.4	P32297-3
	CHRNA3	ENST00000893003.1		c.510-290G>A		intron	N/A	ENSP00000563062.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47406 AN: 151962 Hom.: 8504 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.312 AC: 47411 AN: 152080 Hom.: 8500 Cov.: 32 AF XY: 0.310 AC XY: 23020 AN XY: 74342

African (AFR) AF: 0.151 AC: 6260 AN: 41514

American (AMR) AF: 0.241 AC: 3686 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1259 AN: 3462

East Asian (EAS) AF: 0.192 AC: 990 AN: 5166

South Asian (SAS) AF: 0.319 AC: 1537 AN: 4820

European-Finnish (FIN) AF: 0.377 AC: 3982 AN: 10566

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28614 AN: 67960

Other (OTH) AF: 0.305 AC: 643 AN: 2108

Alfa AF: 0.386 Hom.: 23560

Bravo AF: 0.294

Asia WGS AF: 0.255 AC: 886 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	0.48
DANN	Benign	0.46
PhyloP100		-0.11
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: rs3743077; hg19: chr15-78894896;