rs951266

chr15-78586199-G-Achr15-78586199-G-T

Variant summary

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

The NM_000745.4(CHRNA5):c.259-446G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,044 control chromosomes in the GnomAD database, including 6,004 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 0.26 (6004 hom., cov: 32)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.333

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA5	NM_000745.4	c.259-446G>A		intron_variant		ENST00000299565.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA5	ENST00000299565.9	c.259-446G>A		intron_variant		1	NM_000745.4	P1
CHRNA5	ENST00000394802.4	c.74-446G>A		intron_variant		3
CHRNA5	ENST00000559554.5	c.259-446G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38784 AN: 151926 Hom.: 6004 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.0329

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.290

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.255 AC: 38799 AN: 152044 Hom.: 6004 Cov.: 32 AF XY: 0.252 AC XY: 18739 AN XY: 74330

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.0332

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.288

Alfa AF: 0.315 Hom.: 8793

Bravo AF: 0.240

Asia WGS AF: 0.120 AC: 422 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	0.81
Dann	Benign	0.79

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: rs951266; hg19: chr15-78878541;