15-78589276-T-C

Position:

• chr15-78589276-T-C

Variant summary

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

The NM_000745.4(CHRNA5):​c.414-529T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,332 control chromosomes in the GnomAD database, including 6,721 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 0.28 (6713 hom., cov: 32)
  • Exomes 𝑓: 0.28 (8 hom.)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.414-529T>C		intron_variant		ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9	c.414-529T>C		intron_variant		1	NM_000745.4	ENSP00000299565	P1
	ENST00000567141.1	n.2001A>G		non_coding_transcript_exon_variant	1/1
CHRNA5	ENST00000394802.4	c.229-529T>C		intron_variant		3		ENSP00000378281
CHRNA5	ENST00000559554.5	c.414-529T>C		intron_variant		3		ENSP00000453519

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41899 AN: 152066 Hom.: 6717 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.277 AC: 41 AN: 148 Hom.: 8 Cov.: 0 AF XY: 0.244 AC XY: 19 AN XY: 78

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.327

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.275 AC: 41891 AN: 152184 Hom.: 6713 Cov.: 32 AF XY: 0.275 AC XY: 20434 AN XY: 74410

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.273

Alfa AF: 0.319 Hom.: 2035

Bravo AF: 0.258

Asia WGS AF: 0.237 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.36

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: rs17408276; hg19: chr15-78881618;