rs692780

Variant names:

• chr15-78584163-C-G
• rs692780
• NM_000745.4:c.259-2482C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-78584163-C-G
• chr15-78584163-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.259-2482C>G		intron_variant	Intron 2 of 5	ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9	c.259-2482C>G		intron_variant	Intron 2 of 5	1	NM_000745.4	ENSP00000299565.5
CHRNA5	ENST00000394802.4	c.73-2482C>G		intron_variant	Intron 1 of 4	3		ENSP00000378281.4
CHRNA5	ENST00000559554.5	c.259-2482C>G		intron_variant	Intron 2 of 5	3		ENSP00000453519.1

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

African (AFR) AF: 0.761 AC: 31557 AN: 41488

American (AMR) AF: 0.776 AC: 11854 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2265 AN: 3462

East Asian (EAS) AF: 0.817 AC: 4221 AN: 5166

South Asian (SAS) AF: 0.690 AC: 3323 AN: 4814

European-Finnish (FIN) AF: 0.652 AC: 6861 AN: 10526

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42712 AN: 67958

Other (OTH) AF: 0.714 AC: 1506 AN: 2108

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
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs692780; hg19: chr15-78876505;