rs481134

Variant names:

• chr15-78585221-A-G
• rs481134
• NM_000745.4:c.259-1424A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-78585221-A-G
• chr15-78585221-A-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.259-1424A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 151,986 control chromosomes in the GnomAD database, including 32,195 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 0.65 (32195 hom., cov: 32)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 19 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.259-1424A>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.259-1424A>G		intron_variant	Intron 2 of 5	1	NM_000745.4	ENSP00000299565.5
CHRNA5	ENST00000394802.4	c.73-1424A>G		intron_variant	Intron 1 of 4	3		ENSP00000378281.4
CHRNA5	ENST00000559554.5	c.259-1424A>G		intron_variant	Intron 2 of 5	3		ENSP00000453519.1

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98100 AN: 151866 Hom.: 32143 Cov.: 32

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.646 AC: 98214 AN: 151986 Hom.: 32195 Cov.: 32 AF XY: 0.651 AC XY: 48345 AN XY: 74288

African (AFR) AF: 0.703 AC: 29138 AN: 41428

American (AMR) AF: 0.746 AC: 11391 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2209 AN: 3466

East Asian (EAS) AF: 0.821 AC: 4255 AN: 5184

South Asian (SAS) AF: 0.671 AC: 3226 AN: 4806

European-Finnish (FIN) AF: 0.626 AC: 6617 AN: 10578

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39212 AN: 67932

Other (OTH) AF: 0.674 AC: 1424 AN: 2112

Alfa AF: 0.637 Hom.: 12141

Bravo AF: 0.658

Asia WGS AF: 0.735 AC: 2558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.22
DANN	Benign	0.79
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs481134; hg19: chr15-78877563;