15-78595490-A-G

Variant names:

• chr15-78595490-A-G
• rs660652
• NM_000743.5:c.*1114T>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.*1114T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 779,062 control chromosomes in the GnomAD database, including 157,907 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 0.68 (35273 hom., cov: 31)
  • Exomes 𝑓: 0.63 (122634 hom.)
• Consequence: CHRNA3 NM_000743.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278
• Publications: 44 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]

CHRNA5 (HGNC:1959): (cholinergic receptor nicotinic alpha 5 subunit) The protein encoded by this gene is a nicotinic acetylcholine receptor subunit and a member of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. These receptors are thought to be heteropentamers composed of separate but similar subunits. Defects in this gene have been linked to susceptibility to lung cancer type 2 (LNCR2).[provided by RefSeq, Jun 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 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.*1114T>C		3_prime_UTR	Exon 6 of 6	NP_000734.2
	CHRNA3	NM_001166694.2		c.1390-2299T>C		intron	N/A	NP_001160166.1	P32297-3
	CHRNA3	NR_046313.2		n.1784+1050T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA3	ENST00000326828.6	TSL:1 MANE Select	c.*1114T>C		3_prime_UTR	Exon 6 of 6	ENSP00000315602.5	P32297-2
	CHRNA3	ENST00000348639.7	TSL:1	c.1390-2299T>C		intron	N/A	ENSP00000267951.4	P32297-3
	CHRNA3	ENST00000559002.5	TSL:1	n.193+1050T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.678 AC: 102993 AN: 151812 Hom.: 35229 Cov.: 31

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.695

GnomAD4 exome AF: 0.627 AC: 393227 AN: 627132 Hom.: 122634 Cov.: 8 AF XY: 0.626 AC XY: 183411 AN XY: 292842

African (AFR) AF: 0.727 AC: 8476 AN: 11652

American (AMR) AF: 0.804 AC: 593 AN: 738

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2521 AN: 3862

East Asian (EAS) AF: 0.826 AC: 2161 AN: 2616

South Asian (SAS) AF: 0.699 AC: 8464 AN: 12106

European-Finnish (FIN) AF: 0.682 AC: 131 AN: 192

Middle Eastern (MID) AF: 0.746 AC: 929 AN: 1246

European-Non Finnish (NFE) AF: 0.621 AC: 356751 AN: 574362

Other (OTH) AF: 0.648 AC: 13201 AN: 20358

GnomAD4 genome AF: 0.679 AC: 103097 AN: 151930 Hom.: 35273 Cov.: 31 AF XY: 0.682 AC XY: 50611 AN XY: 74262

African (AFR) AF: 0.715 AC: 29653 AN: 41444

American (AMR) AF: 0.768 AC: 11717 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2265 AN: 3464

East Asian (EAS) AF: 0.819 AC: 4230 AN: 5166

South Asian (SAS) AF: 0.701 AC: 3375 AN: 4812

European-Finnish (FIN) AF: 0.649 AC: 6838 AN: 10532

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42788 AN: 67944

Other (OTH) AF: 0.699 AC: 1472 AN: 2106

Alfa AF: 0.650 Hom.: 83285

Bravo AF: 0.690

Asia WGS AF: 0.755 AC: 2627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.7
DANN	Benign	0.76
PhyloP100		0.28
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: rs660652; hg19: chr15-78887832;