rs11637635

Variant names:

• chr15-78584808-A-G
• rs11637635
• NM_000745.4:c.259-1837A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-78584808-A-G
• chr15-78584808-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.259-1837A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 152,142 control chromosomes in the GnomAD database, including 35,438 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 0.68 (35438 hom., cov: 32)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 26 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.259-1837A>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.259-1837A>G		intron_variant	Intron 2 of 5	1	NM_000745.4	ENSP00000299565.5
CHRNA5	ENST00000394802.4	c.73-1837A>G		intron_variant	Intron 1 of 4	3		ENSP00000378281.4
CHRNA5	ENST00000559554.5	c.259-1837A>G		intron_variant	Intron 2 of 5	3		ENSP00000453519.1

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103240 AN: 152024 Hom.: 35384 Cov.: 32

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.700

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

GnomAD4 genome AF: 0.679 AC: 103356 AN: 152142 Hom.: 35438 Cov.: 32 AF XY: 0.682 AC XY: 50746 AN XY: 74370

African (AFR) AF: 0.719 AC: 29841 AN: 41504

American (AMR) AF: 0.770 AC: 11775 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2272 AN: 3468

East Asian (EAS) AF: 0.830 AC: 4299 AN: 5180

South Asian (SAS) AF: 0.691 AC: 3332 AN: 4822

European-Finnish (FIN) AF: 0.653 AC: 6895 AN: 10566

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42699 AN: 68000

Other (OTH) AF: 0.703 AC: 1484 AN: 2110

Alfa AF: 0.658 Hom.: 46568

Bravo AF: 0.690

Asia WGS AF: 0.753 AC: 2619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.73
PhyloP100		-1.4
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: rs11637635; hg19: chr15-78877150;