rs637137

Variant names:

• chr15-78581634-T-A
• rs637137
• NM_000745.4:c.258+672T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000745.4(CHRNA5):​c.258+672T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,064 control chromosomes in the GnomAD database, including 7,264 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 0.29 (7264 hom., cov: 33)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.528
• Publications: 37 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.258+672T>A		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.258+672T>A		intron_variant	Intron 2 of 5	1	NM_000745.4	ENSP00000299565.5
CHRNA5	ENST00000394802.4	c.72+672T>A		intron_variant	Intron 1 of 4	3		ENSP00000378281.4
CHRNA5	ENST00000559554.5	c.258+672T>A		intron_variant	Intron 2 of 5	3		ENSP00000453519.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44283 AN: 151944 Hom.: 7237 Cov.: 33

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.292 AC: 44348 AN: 152064 Hom.: 7264 Cov.: 33 AF XY: 0.299 AC XY: 22205 AN XY: 74322

African (AFR) AF: 0.296 AC: 12297 AN: 41486

American (AMR) AF: 0.480 AC: 7334 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 744 AN: 3468

East Asian (EAS) AF: 0.477 AC: 2467 AN: 5176

South Asian (SAS) AF: 0.429 AC: 2071 AN: 4832

European-Finnish (FIN) AF: 0.297 AC: 3128 AN: 10534

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15408 AN: 67978

Other (OTH) AF: 0.311 AC: 656 AN: 2110

Alfa AF: 0.260 Hom.: 688

Bravo AF: 0.306

Asia WGS AF: 0.474 AC: 1634 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.8
DANN	Benign	0.71
PhyloP100		0.53
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: rs637137; hg19: chr15-78873976;