ENST00000299565:c.-76C>G

Variant names:

• chr15-78565644-C-G
• rs55781567
• ENST00000299565:c.-76C>G

Variant summary

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

The ENST00000299565(CHRNA5):​c.-76C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 386,268 control chromosomes in the GnomAD database, including 20,054 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 0.30 (7373 hom., cov: 32)
  • Exomes 𝑓: 0.32 (12681 hom.)
• Consequence: CHRNA5 ENST00000299565 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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 = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.-76C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	ENST00000299565.9	NP_000736.2
CHRNA5	NM_000745.4	c.-76C>G		5_prime_UTR_variant	Exon 1 of 6	ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565	c.-76C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	1	NM_000745.4	ENSP00000299565.5
CHRNA5	ENST00000299565	c.-76C>G		5_prime_UTR_variant	Exon 1 of 6	1	NM_000745.4	ENSP00000299565.5
CHRNA5	ENST00000559554	c.-76C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	3		ENSP00000453519.1
CHRNA5	ENST00000559554	c.-76C>G		5_prime_UTR_variant	Exon 1 of 6	3		ENSP00000453519.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45942 AN: 151668 Hom.: 7361 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.0337

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.320 AC: 74987 AN: 234490 Hom.: 12681 Cov.: 5 AF XY: 0.318 AC XY: 37269 AN XY: 117054

Gnomad4 AFR exome AF: 0.258

Gnomad4 AMR exome AF: 0.228

Gnomad4 ASJ exome AF: 0.347

Gnomad4 EAS exome AF: 0.0229

Gnomad4 SAS exome AF: 0.236

Gnomad4 FIN exome AF: 0.337

Gnomad4 NFE exome AF: 0.334

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.303 AC: 45989 AN: 151778 Hom.: 7373 Cov.: 32 AF XY: 0.299 AC XY: 22153 AN XY: 74168

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.0340

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.321

Alfa AF: 0.320 Hom.: 996

Bravo AF: 0.295

Asia WGS AF: 0.136 AC: 477 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.8
DANN	Benign	0.49

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: rs55781567; hg19: chr15-78857986;