rs667282

Positions:

• chr15-78571130-T-C

Variant summary

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

The NM_000745.4(CHRNA5):​c.106+5305T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,112 control chromosomes in the GnomAD database, including 7,226 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 0.29 (7226 hom., cov: 32)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.889

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.106+5305T>C		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+5305T>C		intron_variant		1	NM_000745.4	ENSP00000299565	P1
CHRNA5	ENST00000559554.5	c.106+5305T>C		intron_variant		3		ENSP00000453519

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44207 AN: 151994 Hom.: 7199 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.291 AC: 44267 AN: 152112 Hom.: 7226 Cov.: 32 AF XY: 0.298 AC XY: 22175 AN XY: 74348

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.309

Alfa AF: 0.244 Hom.: 7954

Bravo AF: 0.305

Asia WGS AF: 0.475 AC: 1651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.53
DANN	Benign	0.42

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: rs667282; hg19: chr15-78863472;