rs8042059

chr15-78615517-A-Cchr15-78615517-A-T

Variant summary

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

The NM_000743.5(CHRNA3):c.377+1507T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 151,988 control chromosomes in the GnomAD database, including 8,037 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 (8037 hom., cov: 31)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA3	NM_000743.5	c.377+1507T>G		intron_variant		ENST00000326828.6
CHRNA3	NM_001166694.2	c.377+1507T>G		intron_variant
CHRNA3	XM_006720382.4	c.176+1507T>G		intron_variant
CHRNA3	NR_046313.2	n.579+1507T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA3	ENST00000326828.6	c.377+1507T>G		intron_variant		1	NM_000743.5	P1
CHRNA3	ENST00000348639.7	c.377+1507T>G		intron_variant		1
CHRNA3	ENST00000559658.5	c.377+1507T>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45646 AN: 151870 Hom.: 8011 Cov.: 31

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.301 AC: 45713 AN: 151988 Hom.: 8037 Cov.: 31 AF XY: 0.309 AC XY: 22945 AN XY: 74272

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.713

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.305

Alfa AF: 0.208 Hom.: 704

Bravo AF: 0.316

Asia WGS AF: 0.571 AC: 1984 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.14
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: rs8042059; hg19: chr15-78907859;