rs871058

chr15-78566149-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000745.4(CHRNA5):c.106+324G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 151,980 control chromosomes in the GnomAD database, including 5,629 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 0.24 (5629 hom., cov: 31)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA5	NM_000745.4	c.106+324G>A		intron_variant		ENST00000299565.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA5	ENST00000299565.9	c.106+324G>A		intron_variant		1	NM_000745.4	P1
CHRNA5	ENST00000559554.5	c.106+324G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36825 AN: 151862 Hom.: 5633 Cov.: 31

Gnomad AFR AF: 0.0684

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.242 AC: 36806 AN: 151980 Hom.: 5629 Cov.: 31 AF XY: 0.240 AC XY: 17806 AN XY: 74278

Gnomad4 AFR AF: 0.0682

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.242

Alfa AF: 0.300 Hom.: 990

Bravo AF: 0.225

Asia WGS AF: 0.180 AC: 624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	4.6
Dann	Benign	0.73

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: rs871058; hg19: chr15-78858491;