15-78602417-C-G

Variant names:

• chr15-78602417-C-G
• rs3743078
• NM_000743.5:c.378-153G>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.378-153G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,016 control chromosomes in the GnomAD database, including 31,134 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 0.61 (31134 hom., cov: 31)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• Publications: 50 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA3	NM_000743.5	c.378-153G>C		intron_variant	Intron 4 of 5	ENST00000326828.6	NP_000734.2
CHRNA3	NM_001166694.2	c.378-153G>C		intron_variant	Intron 4 of 5		NP_001160166.1
CHRNA3	NR_046313.2	n.580-153G>C		intron_variant	Intron 4 of 7
CHRNA3	XM_006720382.4	c.177-153G>C		intron_variant	Intron 4 of 5		XP_006720445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA3	ENST00000326828.6	c.378-153G>C		intron_variant	Intron 4 of 5	1	NM_000743.5	ENSP00000315602.5
CHRNA3	ENST00000348639.7	c.378-153G>C		intron_variant	Intron 4 of 5	1		ENSP00000267951.4
CHRNA3	ENST00000558903.1	n.85-153G>C		intron_variant	Intron 1 of 1	4
CHRNA3	ENST00000559658.5	n.378-153G>C		intron_variant	Intron 4 of 7	2		ENSP00000452896.1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93304 AN: 151898 Hom.: 31128 Cov.: 31

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.614 AC: 93333 AN: 152016 Hom.: 31134 Cov.: 31 AF XY: 0.606 AC XY: 45051 AN XY: 74308

African (AFR) AF: 0.419 AC: 17378 AN: 41434

American (AMR) AF: 0.491 AC: 7508 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2622 AN: 3472

East Asian (EAS) AF: 0.224 AC: 1157 AN: 5158

South Asian (SAS) AF: 0.541 AC: 2604 AN: 4814

European-Finnish (FIN) AF: 0.705 AC: 7442 AN: 10558

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.770 AC: 52356 AN: 67990

Other (OTH) AF: 0.623 AC: 1315 AN: 2112

Alfa AF: 0.591 Hom.: 1952

Bravo AF: 0.587

Asia WGS AF: 0.381 AC: 1327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.50
PhyloP100		-0.15
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: rs3743078; hg19: chr15-78894759;