15-78615394-G-A

Variant names:

• chr15-78615394-G-A
• rs12443170
• NM_000743.5:c.377+1630C>T

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+1630C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,152 control chromosomes in the GnomAD database, including 1,430 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 0.12 (1430 hom., cov: 32)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352
• Publications: 18 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 (SAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA3	NM_000743.5	c.377+1630C>T		intron_variant	Intron 4 of 5	ENST00000326828.6	NP_000734.2
CHRNA3	NM_001166694.2	c.377+1630C>T		intron_variant	Intron 4 of 5		NP_001160166.1
CHRNA3	NR_046313.2	n.579+1630C>T		intron_variant	Intron 4 of 7
CHRNA3	XM_006720382.4	c.176+1630C>T		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.377+1630C>T		intron_variant	Intron 4 of 5	1	NM_000743.5	ENSP00000315602.5
CHRNA3	ENST00000348639.7	c.377+1630C>T		intron_variant	Intron 4 of 5	1		ENSP00000267951.4
CHRNA3	ENST00000559658.5	n.377+1630C>T		intron_variant	Intron 4 of 7	2		ENSP00000452896.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18161 AN: 152034 Hom.: 1427 Cov.: 32

Gnomad AFR AF: 0.0414

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0831

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.119 AC: 18171 AN: 152152 Hom.: 1430 Cov.: 32 AF XY: 0.125 AC XY: 9297 AN XY: 74368

African (AFR) AF: 0.0414 AC: 1719 AN: 41548

American (AMR) AF: 0.188 AC: 2870 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 376 AN: 3470

East Asian (EAS) AF: 0.0829 AC: 429 AN: 5172

South Asian (SAS) AF: 0.328 AC: 1580 AN: 4822

European-Finnish (FIN) AF: 0.161 AC: 1706 AN: 10584

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9164 AN: 67972

Other (OTH) AF: 0.121 AC: 255 AN: 2106

Alfa AF: 0.116 Hom.: 755

Bravo AF: 0.112

Asia WGS AF: 0.217 AC: 753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.84
PhyloP100		-0.35
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: rs12443170; hg19: chr15-78907736;