rs667282

Variant names:

• chr15-78571130-T-C
• rs667282
• NM_000745.4:c.106+5305T>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.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
• Publications: 59 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000745.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA5	NM_000745.4	MANE Select	c.106+5305T>C		intron	N/A	NP_000736.2
	CHRNA5	NM_001395171.1		c.106+5305T>C		intron	N/A	NP_001382100.1
	CHRNA5	NM_001395172.1		c.106+5305T>C		intron	N/A	NP_001382101.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA5	ENST00000299565.9	TSL:1 MANE Select	c.106+5305T>C		intron	N/A	ENSP00000299565.5
	CHRNA5	ENST00000559554.5	TSL:3	c.106+5305T>C		intron	N/A	ENSP00000453519.1

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

African (AFR) AF: 0.294 AC: 12219 AN: 41500

American (AMR) AF: 0.480 AC: 7328 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 754 AN: 3470

East Asian (EAS) AF: 0.477 AC: 2462 AN: 5166

South Asian (SAS) AF: 0.428 AC: 2067 AN: 4824

European-Finnish (FIN) AF: 0.296 AC: 3129 AN: 10570

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15411 AN: 67988

Other (OTH) AF: 0.309 AC: 654 AN: 2114

Alfa AF: 0.258 Hom.: 15762

Bravo AF: 0.305

Asia WGS AF: 0.475 AC: 1651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.53
DANN	Benign	0.42
PhyloP100		-0.89
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: rs667282; hg19: chr15-78863472;