rs17486278

chr15-78575140-A-C

Variant summary

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

The NM_000745.4(CHRNA5):c.107-5671A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 151,934 control chromosomes in the GnomAD database, including 7,842 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 0.32 (7842 hom., cov: 31)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.567

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA5	NM_000745.4	c.107-5671A>C		intron_variant		ENST00000299565.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA5	ENST00000299565.9	c.107-5671A>C		intron_variant		1	NM_000745.4	P1
CHRNA5	ENST00000559554.5	c.107-5671A>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48132 AN: 151818 Hom.: 7832 Cov.: 31

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.317 AC: 48182 AN: 151934 Hom.: 7842 Cov.: 31 AF XY: 0.314 AC XY: 23345 AN XY: 74264

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.334

Alfa AF: 0.303 Hom.: 1460

Bravo AF: 0.311

Asia WGS AF: 0.226 AC: 789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.95
Dann	Benign	0.75

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: rs17486278; hg19: chr15-78867482;