15-78600442-G-A

Variant names:

• chr15-78600442-G-A
• rs62010327
• NM_000743.5:c.1389+811C>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+811C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,046 control chromosomes in the GnomAD database, including 6,567 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 0.27 (6567 hom., cov: 32)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA3	NM_000743.5	c.1389+811C>T		intron_variant	Intron 5 of 5	ENST00000326828.6	NP_000734.2
CHRNA3	NM_001166694.2	c.1389+811C>T		intron_variant	Intron 5 of 5		NP_001160166.1
CHRNA3	NR_046313.2	n.1591+811C>T		intron_variant	Intron 5 of 7
CHRNA3	XM_006720382.4	c.1188+811C>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+811C>T		intron_variant	Intron 5 of 5	1	NM_000743.5	ENSP00000315602.5
CHRNA3	ENST00000348639.7	c.1389+811C>T		intron_variant	Intron 5 of 5	1		ENSP00000267951.4
CHRNA3	ENST00000559658.5	n.1389+811C>T		intron_variant	Intron 5 of 7	2		ENSP00000452896.1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41271 AN: 151928 Hom.: 6571 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.271 AC: 41259 AN: 152046 Hom.: 6567 Cov.: 32 AF XY: 0.270 AC XY: 20053 AN XY: 74328

African (AFR) AF: 0.116 AC: 4828 AN: 41484

American (AMR) AF: 0.216 AC: 3294 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1194 AN: 3470

East Asian (EAS) AF: 0.141 AC: 728 AN: 5180

South Asian (SAS) AF: 0.293 AC: 1414 AN: 4820

European-Finnish (FIN) AF: 0.337 AC: 3549 AN: 10542

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25269 AN: 67956

Other (OTH) AF: 0.267 AC: 563 AN: 2110

Alfa AF: 0.289 Hom.: 1502

Bravo AF: 0.254

Asia WGS AF: 0.206 AC: 717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.6
DANN	Benign	0.47
PhyloP100		0.15
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: rs62010327; hg19: chr15-78892784;