rs692780

chr15-78584163-C-Gchr15-78584163-C-T

Variant summary

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

The NM_000745.4(CHRNA5):c.259-2482C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 152,000 control chromosomes in the GnomAD database, including 36,723 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 0.69 (36723 hom., cov: 31)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA5	NM_000745.4	c.259-2482C>G		intron_variant		ENST00000299565.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA5	ENST00000299565.9	c.259-2482C>G		intron_variant		1	NM_000745.4	P1
CHRNA5	ENST00000394802.4	c.74-2482C>G		intron_variant		3
CHRNA5	ENST00000559554.5	c.259-2482C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104950 AN: 151882 Hom.: 36669 Cov.: 31

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.691 AC: 105068 AN: 152000 Hom.: 36723 Cov.: 31 AF XY: 0.693 AC XY: 51492 AN XY: 74268

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.817

Gnomad4 SAS AF: 0.690

Gnomad4 FIN AF: 0.652

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.714

Alfa AF: 0.648 Hom.: 3810

Bravo AF: 0.704

Asia WGS AF: 0.751 AC: 2613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.17
Dann	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs692780; hg19: chr15-78876505;