chr15-78565554-T-A

Position:

• chr15-78565554-T-A

Variant summary

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

The NM_000745.4(CHRNA5):​c.-166T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 215,114 control chromosomes in the GnomAD database, including 9,738 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 (7122 hom., cov: 33)
  • Exomes 𝑓: 0.27 (2616 hom.)
• Consequence: CHRNA5 NM_000745.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA5	NM_000745.4	c.-166T>A		5_prime_UTR_variant	1/6	ENST00000299565.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA5	ENST00000299565.9	c.-166T>A		5_prime_UTR_variant	1/6	1	NM_000745.4	P1
CHRNA5	ENST00000559554.5			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43809 AN: 151910 Hom.: 7097 Cov.: 33

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.327

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.299

GnomAD4 exome AF: 0.273 AC: 17229 AN: 63098 Hom.: 2616 Cov.: 0 AF XY: 0.274 AC XY: 9369 AN XY: 34222

Gnomad4 AFR exome AF: 0.277

Gnomad4 AMR exome AF: 0.543

Gnomad4 ASJ exome AF: 0.269

Gnomad4 EAS exome AF: 0.520

Gnomad4 SAS exome AF: 0.505

Gnomad4 FIN exome AF: 0.301

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.306

GnomAD4 genome AF: 0.289 AC: 43860 AN: 152016 Hom.: 7122 Cov.: 33 AF XY: 0.299 AC XY: 22184 AN XY: 74312

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.307

Alfa AF: 0.258 Hom.: 688

Bravo AF: 0.300

Asia WGS AF: 0.489 AC: 1694 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.3
DANN	Benign	0.60

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: rs503464; hg19: chr15-78857896;