rs1051730

Variant names:

• chr15-78601997-G-A
• rs1051730
• NM_000743.5:c.645C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-78601997-G-A
• chr15-78601997-G-C
• chr15-78601997-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000743.5(CHRNA3):​c.645C>T​(p.Tyr215Tyr) 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
• Publications: 577 publications found

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]

CHRNA3 Gene-Disease associations (from GenCC):

• urinary bladder, atony of

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
CHRNA3	NM_000743.5	c.645C>T	p.Tyr215Tyr	synonymous_variant	Exon 5 of 6	ENST00000326828.6	NP_000734.2
CHRNA3	NM_001166694.2	c.645C>T	p.Tyr215Tyr	synonymous_variant	Exon 5 of 6		NP_001160166.1
CHRNA3	XM_006720382.4	c.444C>T	p.Tyr148Tyr	synonymous_variant	Exon 5 of 6		XP_006720445.1
CHRNA3	NR_046313.2	n.847C>T		non_coding_transcript_exon_variant	Exon 5 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA3	ENST00000326828.6	c.645C>T	p.Tyr215Tyr	synonymous_variant	Exon 5 of 6	1	NM_000743.5	ENSP00000315602.5
CHRNA3	ENST00000348639.7	c.645C>T	p.Tyr215Tyr	synonymous_variant	Exon 5 of 6	1		ENSP00000267951.4
CHRNA3	ENST00000558903.1	n.352C>T		non_coding_transcript_exon_variant	Exon 2 of 2	4
CHRNA3	ENST00000559658.5	n.645C>T		non_coding_transcript_exon_variant	Exon 5 of 8	2		ENSP00000452896.1

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

GnomAD2 exomes AF: 0.269 AC: 67652 AN: 251254 AF XY: 0.279

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 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

African (AFR) AF: 0.110 AC: 3682 AN: 33468

American (AMR) AF: 0.176 AC: 7865 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 9979 AN: 26132

East Asian (EAS) AF: 0.0265 AC: 1050 AN: 39680

South Asian (SAS) AF: 0.239 AC: 20578 AN: 86240

European-Finnish (FIN) AF: 0.330 AC: 17619 AN: 53410

Middle Eastern (MID) AF: 0.377 AC: 2173 AN: 5768

European-Non Finnish (NFE) AF: 0.335 AC: 372463 AN: 1111468

Other (OTH) AF: 0.295 AC: 17829 AN: 60368

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

African (AFR) AF: 0.118 AC: 4902 AN: 41432

American (AMR) AF: 0.234 AC: 3566 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1318 AN: 3468

East Asian (EAS) AF: 0.0323 AC: 167 AN: 5168

South Asian (SAS) AF: 0.220 AC: 1057 AN: 4798

European-Finnish (FIN) AF: 0.326 AC: 3431 AN: 10526

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23626 AN: 67902

Other (OTH) AF: 0.292 AC: 617 AN: 2110

Alfa AF: 0.308 Hom.: 22880

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Lung cancer susceptibility 2 Other:1

May 01, 2008

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

SMOKING AS A QUANTITATIVE TRAIT LOCUS 3 Other:1

May 01, 2008

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	8.6
DANN	Benign	0.56
PhyloP100		5.5
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

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