rs684513

Positions:

• chr15-78566058-C-G
• chr15-78566058-C-T

Variant summary

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

The NM_000745.4(CHRNA5):​c.106+233C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,056 control chromosomes in the GnomAD database, including 4,489 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 0.23 (4489 hom., cov: 31)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.106+233C>G		intron_variant		ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9	c.106+233C>G		intron_variant		1	NM_000745.4	ENSP00000299565	P1
CHRNA5	ENST00000559554.5	c.106+233C>G		intron_variant		3		ENSP00000453519

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35079 AN: 151938 Hom.: 4475 Cov.: 31

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.231 AC: 35117 AN: 152056 Hom.: 4489 Cov.: 31 AF XY: 0.237 AC XY: 17628 AN XY: 74324

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.243

Alfa AF: 0.107 Hom.: 159

Bravo AF: 0.239

Asia WGS AF: 0.305 AC: 1061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.2
DANN	Benign	0.54

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: rs684513; hg19: chr15-78858400;