rs518425

Variant names:

• chr15-78591471-A-G
• rs518425
• NM_000745.4:c.1245+835A>G

Variant summary

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

The NM_000745.4(CHRNA5):​c.1245+835A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,558 control chromosomes in the GnomAD database, including 12,966 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 (12966 hom., cov: 31)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 29 publications found

Genes affected

CHRNA5 (HGNC:1959): (cholinergic receptor nicotinic alpha 5 subunit) The protein encoded by this gene is a nicotinic acetylcholine receptor subunit and a member of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. These receptors are thought to be heteropentamers composed of separate but similar subunits. Defects in this gene have been linked to susceptibility to lung cancer type 2 (LNCR2).[provided by RefSeq, Jun 2010]

ENSG00000261762 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) 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
CHRNA5	NM_000745.4	c.1245+835A>G		intron_variant	Intron 5 of 5	ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9	c.1245+835A>G		intron_variant	Intron 5 of 5	1	NM_000745.4	ENSP00000299565.5

Frequencies

GnomAD3 genomes AF: 0.389 AC: 58973 AN: 151438 Hom.: 12935 Cov.: 31

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.390 AC: 59045 AN: 151558 Hom.: 12966 Cov.: 31 AF XY: 0.396 AC XY: 29306 AN XY: 74050

African (AFR) AF: 0.492 AC: 20315 AN: 41304

American (AMR) AF: 0.524 AC: 7977 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 913 AN: 3462

East Asian (EAS) AF: 0.787 AC: 4069 AN: 5172

South Asian (SAS) AF: 0.479 AC: 2306 AN: 4818

European-Finnish (FIN) AF: 0.324 AC: 3373 AN: 10400

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19015 AN: 67866

Other (OTH) AF: 0.387 AC: 812 AN: 2100

Alfa AF: 0.328 Hom.: 5429

Bravo AF: 0.410

Asia WGS AF: 0.626 AC: 2172 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.8
DANN	Benign	0.68
PhyloP100		1.4
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: rs518425; hg19: chr15-78883813;