15-78606381-C-T

Variant names:

• chr15-78606381-C-T
• rs12914385
• NM_000743.5:c.378-4117G>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.378-4117G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 148,198 control chromosomes in the GnomAD database, including 7,838 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 (7838 hom., cov: 27)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233
• Publications: 134 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.389 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.378-4117G>A		intron	N/A	NP_000734.2
	CHRNA3	NM_001166694.2		c.378-4117G>A		intron	N/A	NP_001160166.1	P32297-3
	CHRNA3	NR_046313.2		n.580-4117G>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.378-4117G>A		intron	N/A	ENSP00000315602.5	P32297-2
	CHRNA3	ENST00000348639.7	TSL:1	c.378-4117G>A		intron	N/A	ENSP00000267951.4	P32297-3
	CHRNA3	ENST00000893003.1		c.510-4117G>A		intron	N/A	ENSP00000563062.1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 46014 AN: 148104 Hom.: 7835 Cov.: 27

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.431

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.311 AC: 46045 AN: 148198 Hom.: 7838 Cov.: 27 AF XY: 0.306 AC XY: 21990 AN XY: 71886

African (AFR) AF: 0.185 AC: 7478 AN: 40330

American (AMR) AF: 0.257 AC: 3811 AN: 14804

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1425 AN: 3438

East Asian (EAS) AF: 0.276 AC: 1401 AN: 5074

South Asian (SAS) AF: 0.238 AC: 1128 AN: 4730

European-Finnish (FIN) AF: 0.342 AC: 3142 AN: 9186

Middle Eastern (MID) AF: 0.418 AC: 118 AN: 282

European-Non Finnish (NFE) AF: 0.393 AC: 26471 AN: 67412

Other (OTH) AF: 0.335 AC: 685 AN: 2042

Alfa AF: 0.360 Hom.: 46064

Bravo AF: 0.301

Asia WGS AF: 0.222 AC: 775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.3
DANN	Benign	0.52
PhyloP100		-0.23
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: rs12914385; hg19: chr15-78898723;