rs4243084

Positions:

• chr15-78619330-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000326828.6(CHRNA3):​c.83-415C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 197,522 control chromosomes in the GnomAD database, including 9,334 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 0.30 (7162 hom., cov: 33)
  • Exomes 𝑓: 0.29 (2172 hom.)
• Consequence: CHRNA3 ENST00000326828.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.414

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA3	NM_000743.5	c.83-415C>G		intron_variant		ENST00000326828.6	NP_000734.2
CHRNA3	NM_001166694.2	c.83-415C>G		intron_variant			NP_001160166.1
CHRNA3	XM_006720382.4	c.-120+407C>G		intron_variant			XP_006720445.1
CHRNA3	NR_046313.2	n.285-415C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA3	ENST00000326828.6	c.83-415C>G		intron_variant		1	NM_000743.5	ENSP00000315602	P1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45093 AN: 152078 Hom.: 7161 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.327

GnomAD4 exome AF: 0.294 AC: 13312 AN: 45326 Hom.: 2172 AF XY: 0.288 AC XY: 6779 AN XY: 23504

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.251

Gnomad4 ASJ exome AF: 0.359

Gnomad4 EAS exome AF: 0.257

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.324

Gnomad4 NFE exome AF: 0.317

Gnomad4 OTH exome AF: 0.305

GnomAD4 genome AF: 0.296 AC: 45121 AN: 152196 Hom.: 7162 Cov.: 33 AF XY: 0.294 AC XY: 21902 AN XY: 74404

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.325

Alfa AF: 0.312 Hom.: 965

Bravo AF: 0.286

Asia WGS AF: 0.217 AC: 757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.84
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs4243084; hg19: chr15-78911672; COSMIC: COSV55717710; COSMIC: COSV55717710;