rs1051730

chr15-78601997-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000743.5(CHRNA3):c.645C>T(p.Tyr215=) variant causes a synonymous change. The variant allele was found at a frequency of 0.305 in 1,613,104 control chromosomes in the GnomAD database, including 80,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (6058 hom., cov: 31)
  • Exomes 𝑓: 0.31 (74434 hom.)
• Consequence: CHRNA3 NM_000743.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1 O:2
• Conservation: PhyloP100: 5.50

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 15-78601997-G-A is Benign according to our data. Variant chr15-78601997-G-A is described in ClinVar as [Benign]. Clinvar id is 17503.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA3	NM_000743.5	c.645C>T	p.Tyr215=	synonymous_variant	5/6	ENST00000326828.6
CHRNA3	NM_001166694.2	c.645C>T	p.Tyr215=	synonymous_variant	5/6
CHRNA3	XM_006720382.4	c.444C>T	p.Tyr148=	synonymous_variant	5/6
CHRNA3	NR_046313.2	n.847C>T		non_coding_transcript_exon_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA3	ENST00000326828.6	c.645C>T	p.Tyr215=	synonymous_variant	5/6	1	NM_000743.5	P1
CHRNA3	ENST00000348639.7	c.645C>T	p.Tyr215=	synonymous_variant	5/6	1
CHRNA3	ENST00000558903.1	n.352C>T		non_coding_transcript_exon_variant	2/2	4
CHRNA3	ENST00000559658.5	c.645C>T	p.Tyr215=	synonymous_variant, NMD_transcript_variant	5/8	2

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39177 AN: 151744 Hom.: 6060 Cov.: 31

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.0320

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.295

GnomAD3 exomes AF: 0.269 AC: 67652 AN: 251254 Hom.: 10777 AF XY: 0.279 AC XY: 37940 AN XY: 135766

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.166

Gnomad ASJ exome AF: 0.383

Gnomad EAS exome AF: 0.0322

Gnomad SAS exome AF: 0.236

Gnomad FIN exome AF: 0.321

Gnomad NFE exome AF: 0.349

Gnomad OTH exome AF: 0.299

GnomAD4 exome AF: 0.310 AC: 453238 AN: 1461244 Hom.: 74434 Cov.: 42 AF XY: 0.310 AC XY: 225164 AN XY: 726806

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.176

Gnomad4 ASJ exome AF: 0.382

Gnomad4 EAS exome AF: 0.0265

Gnomad4 SAS exome AF: 0.239

Gnomad4 FIN exome AF: 0.330

Gnomad4 NFE exome AF: 0.335

Gnomad4 OTH exome AF: 0.295

GnomAD4 genome AF: 0.258 AC: 39187 AN: 151860 Hom.: 6058 Cov.: 31 AF XY: 0.254 AC XY: 18879 AN XY: 74220

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.0323

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.292

Alfa AF: 0.324 Hom.: 15344

Bravo AF: 0.244

Asia WGS AF: 0.117 AC: 412 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Lung cancer susceptibility 2 Other:1

risk factor, no assertion criteria provided

literature only

OMIM

May 01, 2008

- -

Smoking as a quantitative trait locus 3 Other:1

risk factor, no assertion criteria provided

literature only

OMIM

May 01, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	8.6
Dann	Benign	0.56

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: rs1051730; hg19: chr15-78894339; COSMIC: COSV58774115; COSMIC: COSV58774115;