rs3743073

Variant names:

• chr15-78617197-G-T
• rs3743073
• NM_000743.5:c.268-64C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-78617197-G-T
• chr15-78617197-G-A
• chr15-78617197-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000743.5(CHRNA3):​c.268-64C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 1,084,310 control chromosomes in the GnomAD database, including 210,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (28919 hom., cov: 32)
  • Exomes 𝑓: 0.62 (181188 hom.)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.10
• Publications: 34 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 15-78617197-G-T is Benign according to our data. Variant chr15-78617197-G-T is described in ClinVar as Benign. ClinVar VariationId is 1209769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.734 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA3	NM_000743.5	MANE Select	c.268-64C>A		intron	N/A	NP_000734.2
	CHRNA3	NM_001166694.2		c.268-64C>A		intron	N/A	NP_001160166.1	P32297-3
	CHRNA3	NR_046313.2		n.470-64C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA3	ENST00000326828.6	TSL:1 MANE Select	c.268-64C>A		intron	N/A	ENSP00000315602.5	P32297-2
	CHRNA3	ENST00000348639.7	TSL:1	c.268-64C>A		intron	N/A	ENSP00000267951.4	P32297-3
	CHRNA3	ENST00000893003.1		c.400-64C>A		intron	N/A	ENSP00000563062.1

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92945 AN: 151822 Hom.: 28879 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.642

GnomAD4 exome AF: 0.620 AC: 577958 AN: 932368 Hom.: 181188 AF XY: 0.622 AC XY: 298227 AN XY: 479542

African (AFR) AF: 0.519 AC: 12250 AN: 23598

American (AMR) AF: 0.816 AC: 29774 AN: 36478

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 13564 AN: 21318

East Asian (EAS) AF: 0.569 AC: 20506 AN: 36028

South Asian (SAS) AF: 0.681 AC: 47388 AN: 69590

European-Finnish (FIN) AF: 0.651 AC: 30336 AN: 46624

Middle Eastern (MID) AF: 0.714 AC: 3337 AN: 4674

European-Non Finnish (NFE) AF: 0.605 AC: 394181 AN: 651080

Other (OTH) AF: 0.619 AC: 26622 AN: 42978

GnomAD4 genome AF: 0.612 AC: 93029 AN: 151942 Hom.: 28919 Cov.: 32 AF XY: 0.614 AC XY: 45630 AN XY: 74272

African (AFR) AF: 0.523 AC: 21662 AN: 41404

American (AMR) AF: 0.746 AC: 11397 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2211 AN: 3466

East Asian (EAS) AF: 0.559 AC: 2873 AN: 5142

South Asian (SAS) AF: 0.675 AC: 3259 AN: 4826

European-Finnish (FIN) AF: 0.651 AC: 6871 AN: 10554

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.627 AC: 42632 AN: 67954

Other (OTH) AF: 0.647 AC: 1363 AN: 2106

Alfa AF: 0.607 Hom.: 3242

Bravo AF: 0.614

Asia WGS AF: 0.635 AC: 2209 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Urinary bladder, atony of (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.73
PhyloP100		-1.1
Mutation Taster		=100/0	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: rs3743073; hg19: chr15-78909539;