rs71581741

Variant names:

• chr15-78617016-C-G
• rs71581741
• NM_000743.5:c.377+8G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-78617016-C-G
• chr15-78617016-C-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.377+8G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,604,428 control chromosomes in the GnomAD database, including 790 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.040 (367 hom., cov: 32)
  • Exomes 𝑓: 0.0074 (423 hom.)
• Consequence: CHRNA3 NM_000743.5 splice_region, intron
• Scores: Splicing: ADA: 0.0003934
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0360
• Publications: 5 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=-0.71).
• BP6: Variant 15-78617016-C-G is Benign according to our data. Variant chr15-78617016-C-G is described in ClinVar as Benign. ClinVar VariationId is 2039314.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000743.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA3	NM_000743.5	MANE Select	c.377+8G>C		splice_region intron	N/A	NP_000734.2
	CHRNA3	NM_001166694.2		c.377+8G>C		splice_region intron	N/A	NP_001160166.1
	CHRNA3	NR_046313.2		n.579+8G>C		splice_region intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA3	ENST00000326828.6	TSL:1 MANE Select	c.377+8G>C		splice_region intron	N/A	ENSP00000315602.5
	CHRNA3	ENST00000348639.7	TSL:1	c.377+8G>C		splice_region intron	N/A	ENSP00000267951.4
	CHRNA3	ENST00000559658.5	TSL:2	n.377+8G>C		splice_region intron	N/A	ENSP00000452896.1

Frequencies

GnomAD3 genomes AF: 0.0399 AC: 6072 AN: 152202 Hom.: 367 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.0668

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00184

Gnomad OTH AF: 0.0320

GnomAD2 exomes AF: 0.0168 AC: 4156 AN: 247692 AF XY: 0.0142

Gnomad AFR exome AF: 0.129

Gnomad AMR exome AF: 0.00712

Gnomad ASJ exome AF: 0.0196

Gnomad EAS exome AF: 0.0729

Gnomad FIN exome AF: 0.0000946

Gnomad NFE exome AF: 0.00190

Gnomad OTH exome AF: 0.00972

GnomAD4 exome AF: 0.00743 AC: 10786 AN: 1452108 Hom.: 423 Cov.: 29 AF XY: 0.00680 AC XY: 4911 AN XY: 722626

African (AFR) AF: 0.132 AC: 4389 AN: 33280

American (AMR) AF: 0.00770 AC: 343 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 554 AN: 25996

East Asian (EAS) AF: 0.0660 AC: 2617 AN: 39648

South Asian (SAS) AF: 0.00192 AC: 164 AN: 85498

European-Finnish (FIN) AF: 0.0000377 AC: 2 AN: 53082

Middle Eastern (MID) AF: 0.00955 AC: 49 AN: 5130

European-Non Finnish (NFE) AF: 0.00158 AC: 1750 AN: 1104890

Other (OTH) AF: 0.0153 AC: 918 AN: 60066

GnomAD4 genome AF: 0.0399 AC: 6077 AN: 152320 Hom.: 367 Cov.: 32 AF XY: 0.0396 AC XY: 2950 AN XY: 74482

African (AFR) AF: 0.125 AC: 5207 AN: 41548

American (AMR) AF: 0.0149 AC: 228 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0233 AC: 81 AN: 3472

East Asian (EAS) AF: 0.0666 AC: 345 AN: 5182

South Asian (SAS) AF: 0.00435 AC: 21 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00184 AC: 125 AN: 68042

Other (OTH) AF: 0.0317 AC: 67 AN: 2114

Alfa AF: 0.0159 Hom.: 39

Bravo AF: 0.0449

Asia WGS AF: 0.0330 AC: 114 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.6
DANN	Benign	0.76
PhyloP100		-0.036
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00039
dbscSNV1_RF	Benign	0.016
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: rs71581741; hg19: chr15-78909358; COSMIC: COSV58777066; COSMIC: COSV58777066;