rs55853698

chr15-78565597-T-G

Variant summary

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

The NM_000745.4(CHRNA5):c.-123T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 238,140 control chromosomes in the GnomAD database, including 10,646 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 0.25 (5904 hom., cov: 32)
  • Exomes 𝑓: 0.32 (4742 hom.)
• Consequence: CHRNA5 NM_000745.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA5	NM_000745.4	c.-123T>G		5_prime_UTR_variant	1/6	ENST00000299565.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA5	ENST00000299565.9	c.-123T>G		5_prime_UTR_variant	1/6	1	NM_000745.4	P1
CHRNA5	ENST00000559554.5	c.-123T>G		5_prime_UTR_variant	1/6	3

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37692 AN: 151938 Hom.: 5903 Cov.: 32

Gnomad AFR AF: 0.0820

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.0336

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.324 AC: 27866 AN: 86092 Hom.: 4742 Cov.: 3 AF XY: 0.322 AC XY: 14664 AN XY: 45600

Gnomad4 AFR exome AF: 0.0770

Gnomad4 AMR exome AF: 0.217

Gnomad4 ASJ exome AF: 0.341

Gnomad4 EAS exome AF: 0.0246

Gnomad4 SAS exome AF: 0.216

Gnomad4 FIN exome AF: 0.341

Gnomad4 NFE exome AF: 0.354

Gnomad4 OTH exome AF: 0.280

GnomAD4 genome AF: 0.248 AC: 37703 AN: 152048 Hom.: 5904 Cov.: 32 AF XY: 0.245 AC XY: 18188 AN XY: 74344

Gnomad4 AFR AF: 0.0820

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.0339

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.273

Alfa AF: 0.306 Hom.: 1581

Bravo AF: 0.232

Asia WGS AF: 0.122 AC: 427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	7.1
Dann	Benign	0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs55853698; hg19: chr15-78857939; COSMIC: COSV55140423;