chr15-78580777-C-T

Position:

• chr15-78580777-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.107-34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,551,828 control chromosomes in the GnomAD database, including 61,055 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 (7090 hom., cov: 32)
  • Exomes 𝑓: 0.26 (53965 hom.)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.107-34C>T		intron_variant		ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9	c.107-34C>T		intron_variant		1	NM_000745.4	ENSP00000299565.5
CHRNA5	ENST00000559554.5	c.107-34C>T		intron_variant		3		ENSP00000453519.1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43734 AN: 151726 Hom.: 7064 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.297

GnomAD3 exomes AF: 0.339 AC: 80363 AN: 236732 Hom.: 16696 AF XY: 0.332 AC XY: 42474 AN XY: 127996

Gnomad AFR exome AF: 0.290

Gnomad AMR exome AF: 0.645

Gnomad ASJ exome AF: 0.236

Gnomad EAS exome AF: 0.469

Gnomad SAS exome AF: 0.438

Gnomad FIN exome AF: 0.305

Gnomad NFE exome AF: 0.226

Gnomad OTH exome AF: 0.314

GnomAD4 exome AF: 0.259 AC: 362273 AN: 1399984 Hom.: 53965 Cov.: 24 AF XY: 0.263 AC XY: 183234 AN XY: 696902

Gnomad4 AFR exome AF: 0.284

Gnomad4 AMR exome AF: 0.623

Gnomad4 ASJ exome AF: 0.220

Gnomad4 EAS exome AF: 0.502

Gnomad4 SAS exome AF: 0.422

Gnomad4 FIN exome AF: 0.295

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.273

GnomAD4 genome AF: 0.288 AC: 43793 AN: 151844 Hom.: 7090 Cov.: 32 AF XY: 0.296 AC XY: 21950 AN XY: 74188

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.305

Alfa AF: 0.258 Hom.: 1852

Bravo AF: 0.302

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	-0.89
CADD	Benign	1.6
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs569207; hg19: chr15-78873119; COSMIC: COSV55137493; COSMIC: COSV55137493;