rs7180002

Positions:

• chr15-78581651-A-T

Variant summary

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

The NM_000745.4(CHRNA5):​c.258+689A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,138 control chromosomes in the GnomAD database, including 5,999 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 0.25 (5999 hom., cov: 32)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.824

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA5	NM_000745.4	c.258+689A>T		intron_variant		ENST00000299565.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA5	ENST00000299565.9	c.258+689A>T		intron_variant		1	NM_000745.4	P1
CHRNA5	ENST00000394802.4	c.73+689A>T		intron_variant		3
CHRNA5	ENST00000559554.5	c.258+689A>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38745 AN: 152020 Hom.: 5999 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.0329

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.255 AC: 38760 AN: 152138 Hom.: 5999 Cov.: 32 AF XY: 0.252 AC XY: 18728 AN XY: 74374

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.0331

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.287

Alfa AF: 0.289 Hom.: 867

Bravo AF: 0.240

Asia WGS AF: 0.121 AC: 420 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs7180002; hg19: chr15-78873993;