rs3743076

chr15-78616885-T-Achr15-78616885-T-Cchr15-78616885-T-G

Variant summary

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

The NM_000743.5(CHRNA3):c.377+139A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0247 in 604,794 control chromosomes in the GnomAD database, including 1,405 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 0.028 (227 hom., cov: 32)
  • Exomes 𝑓: 0.024 (1178 hom.)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.990

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA3	NM_000743.5	c.377+139A>T		intron_variant		ENST00000326828.6
CHRNA3	NM_001166694.2	c.377+139A>T		intron_variant
CHRNA3	XM_006720382.4	c.176+139A>T		intron_variant
CHRNA3	NR_046313.2	n.579+139A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA3	ENST00000326828.6	c.377+139A>T		intron_variant		1	NM_000743.5	P1
CHRNA3	ENST00000348639.7	c.377+139A>T		intron_variant		1
CHRNA3	ENST00000559658.5	c.377+139A>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0282 AC: 4287 AN: 152156 Hom.: 225 Cov.: 32

Gnomad AFR AF: 0.0641

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00805

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.0132

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000985

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.0236 AC: 10664 AN: 452520 Hom.: 1178 AF XY: 0.0221 AC XY: 5264 AN XY: 238398

Gnomad4 AFR exome AF: 0.0635

Gnomad4 AMR exome AF: 0.00542

Gnomad4 ASJ exome AF: 0.0203

Gnomad4 EAS exome AF: 0.268

Gnomad4 SAS exome AF: 0.00763

Gnomad4 FIN exome AF: 0.000262

Gnomad4 NFE exome AF: 0.000924

Gnomad4 OTH exome AF: 0.0219

GnomAD4 genome AF: 0.0283 AC: 4302 AN: 152274 Hom.: 227 Cov.: 32 AF XY: 0.0288 AC XY: 2141 AN XY: 74452

Gnomad4 AFR AF: 0.0643

Gnomad4 AMR AF: 0.00797

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.0133

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000985

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.000380 Hom.: 0

Bravo AF: 0.0321

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.16
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3743076; hg19: chr15-78909227;