rs17486278

Variant names:

• chr15-78575140-A-C
• rs17486278
• NM_000745.4:c.107-5671A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 80 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.107-5671A>C		intron_variant	Intron 1 of 5	ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9	c.107-5671A>C		intron_variant	Intron 1 of 5	1	NM_000745.4	ENSP00000299565.5
CHRNA5	ENST00000559554.5	c.107-5671A>C		intron_variant	Intron 1 of 5	3		ENSP00000453519.1

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

African (AFR) AF: 0.294 AC: 12162 AN: 41434

American (AMR) AF: 0.250 AC: 3817 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1332 AN: 3468

East Asian (EAS) AF: 0.276 AC: 1428 AN: 5176

South Asian (SAS) AF: 0.238 AC: 1144 AN: 4814

European-Finnish (FIN) AF: 0.327 AC: 3453 AN: 10544

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23644 AN: 67938

Other (OTH) AF: 0.334 AC: 705 AN: 2108

Alfa AF: 0.322 Hom.: 13625

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
PhyloP100		-0.57
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: rs17486278; hg19: chr15-78867482;