rs12910984

Variant names:

• chr15-78599285-G-A
• rs12910984
• NM_000743.5:c.1389+1968C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-78599285-G-A
• chr15-78599285-G-C
• chr15-78599285-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000743.5(CHRNA3):​c.1389+1968C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,098 control chromosomes in the GnomAD database, including 37,841 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 0.70 (37841 hom., cov: 32)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347
• Publications: 37 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA3	NM_000743.5	c.1389+1968C>T		intron_variant	Intron 5 of 5	ENST00000326828.6	NP_000734.2
CHRNA3	NM_001166694.2	c.1389+1968C>T		intron_variant	Intron 5 of 5		NP_001160166.1
CHRNA3	NR_046313.2	n.1591+1968C>T		intron_variant	Intron 5 of 7
CHRNA3	XM_006720382.4	c.1188+1968C>T		intron_variant	Intron 5 of 5		XP_006720445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA3	ENST00000326828.6	c.1389+1968C>T		intron_variant	Intron 5 of 5	1	NM_000743.5	ENSP00000315602.5
CHRNA3	ENST00000348639.7	c.1389+1968C>T		intron_variant	Intron 5 of 5	1		ENSP00000267951.4
CHRNA3	ENST00000559658.5	n.1389+1968C>T		intron_variant	Intron 5 of 7	2		ENSP00000452896.1

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106096 AN: 151980 Hom.: 37822 Cov.: 32

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.695

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.698 AC: 106146 AN: 152098 Hom.: 37841 Cov.: 32 AF XY: 0.691 AC XY: 51385 AN XY: 74370

African (AFR) AF: 0.666 AC: 27634 AN: 41480

American (AMR) AF: 0.519 AC: 7921 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2699 AN: 3470

East Asian (EAS) AF: 0.537 AC: 2776 AN: 5172

South Asian (SAS) AF: 0.560 AC: 2692 AN: 4808

European-Finnish (FIN) AF: 0.704 AC: 7455 AN: 10592

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52557 AN: 67990

Other (OTH) AF: 0.687 AC: 1453 AN: 2114

Alfa AF: 0.730 Hom.: 18948

Bravo AF: 0.683

Asia WGS AF: 0.516 AC: 1796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.75
DANN	Benign	0.23
PhyloP100		-0.35
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: rs12910984; hg19: chr15-78891627;