15-78619005-C-T

Variant names:

• chr15-78619005-C-T
• rs71581736
• NM_000743.5:c.83-90G>A

Variant summary

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

The NM_000743.5(CHRNA3):​c.83-90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00369 in 1,423,450 control chromosomes in the GnomAD database, including 116 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 0.016 (55 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (61 hom.)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA3	NM_000743.5	c.83-90G>A		intron_variant	Intron 1 of 5	ENST00000326828.6	NP_000734.2
CHRNA3	NM_001166694.2	c.83-90G>A		intron_variant	Intron 1 of 5		NP_001160166.1
CHRNA3	XM_006720382.4	c.-119-90G>A		intron_variant	Intron 1 of 5		XP_006720445.1
CHRNA3	NR_046313.2	n.285-90G>A		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA3	ENST00000326828.6	c.83-90G>A		intron_variant	Intron 1 of 5	1	NM_000743.5	ENSP00000315602.5

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2442 AN: 152204 Hom.: 55 Cov.: 33

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.00220 AC: 2796 AN: 1271128 Hom.: 61 Cov.: 18 AF XY: 0.00200 AC XY: 1270 AN XY: 635696

Gnomad4 AFR exome AF: 0.0569

Gnomad4 AMR exome AF: 0.00346

Gnomad4 ASJ exome AF: 0.0204

Gnomad4 EAS exome AF: 0.0000516

Gnomad4 SAS exome AF: 0.000213

Gnomad4 FIN exome AF: 0.0000247

Gnomad4 NFE exome AF: 0.000219

Gnomad4 OTH exome AF: 0.00509

GnomAD4 genome AF: 0.0161 AC: 2452 AN: 152322 Hom.: 55 Cov.: 33 AF XY: 0.0154 AC XY: 1148 AN XY: 74488

Gnomad4 AFR AF: 0.0542

Gnomad4 AMR AF: 0.00496

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000573

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00283 Hom.: 0

Bravo AF: 0.0180

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.44

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: rs71581736; hg19: chr15-78911347;