rs518425

Positions:

• chr15-78591471-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CHRNA5	NM_000745.4	c.1245+835A>G		intron_variant		ENST00000299565.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA5	ENST00000299565.9	c.1245+835A>G		intron_variant		1	NM_000745.4	P1
CHRNA5	ENST00000394802.4	c.522+1373A>G		intron_variant		3
CHRNA5	ENST00000559554.5	c.459-1621A>G		intron_variant		3
CHRNA5	ENST00000559576.1	c.145+965A>G		intron_variant		3

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

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.387

Alfa AF: 0.333 Hom.: 3472

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs518425; hg19: chr15-78883813;