15-78597979-C-T

Variant names:

• chr15-78597979-C-T
• rs6495307
• NM_000743.5:c.1390-1247G>A

Variant summary

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

The NM_000743.5(CHRNA3):​c.1390-1247G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,870 control chromosomes in the GnomAD database, including 11,786 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 0.39 (11786 hom., cov: 31)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 31 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.419 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.1390-1247G>A		intron	N/A	NP_000734.2
	CHRNA3	NM_001166694.2		c.1389+3274G>A		intron	N/A	NP_001160166.1	P32297-3
	CHRNA3	NR_046313.2		n.1592-1247G>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.1390-1247G>A		intron	N/A	ENSP00000315602.5	P32297-2
	CHRNA3	ENST00000348639.7	TSL:1	c.1389+3274G>A		intron	N/A	ENSP00000267951.4	P32297-3
	CHRNA3	ENST00000893003.1		c.1522-1247G>A		intron	N/A	ENSP00000563062.1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58858 AN: 151752 Hom.: 11776 Cov.: 31

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.388 AC: 58892 AN: 151870 Hom.: 11786 Cov.: 31 AF XY: 0.383 AC XY: 28457 AN XY: 74228

African (AFR) AF: 0.414 AC: 17121 AN: 41358

American (AMR) AF: 0.267 AC: 4074 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1264 AN: 3470

East Asian (EAS) AF: 0.190 AC: 984 AN: 5170

South Asian (SAS) AF: 0.320 AC: 1541 AN: 4812

European-Finnish (FIN) AF: 0.377 AC: 3978 AN: 10538

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28715 AN: 67946

Other (OTH) AF: 0.356 AC: 751 AN: 2108

Alfa AF: 0.399 Hom.: 16791

Bravo AF: 0.381

Asia WGS AF: 0.273 AC: 950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.66
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: rs6495307; hg19: chr15-78890321;