15-78588139-T-C

Variant names:

• chr15-78588139-T-C
• rs647041
• NM_000745.4:c.304-175T>C

Variant summary

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

The NM_000745.4(CHRNA5):​c.304-175T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 151,944 control chromosomes in the GnomAD database, including 32,287 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 (32287 hom., cov: 31)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 20 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.304-175T>C		intron_variant	Intron 3 of 5	ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9	c.304-175T>C		intron_variant	Intron 3 of 5	1	NM_000745.4	ENSP00000299565.5
CHRNA5	ENST00000394802.4	c.118-175T>C		intron_variant	Intron 2 of 4	3		ENSP00000378281.4
CHRNA5	ENST00000559554.5	c.304-175T>C		intron_variant	Intron 3 of 5	3		ENSP00000453519.1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98259 AN: 151826 Hom.: 32241 Cov.: 31

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.668

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

GnomAD4 genome AF: 0.647 AC: 98364 AN: 151944 Hom.: 32287 Cov.: 31 AF XY: 0.652 AC XY: 48404 AN XY: 74266

African (AFR) AF: 0.707 AC: 29306 AN: 41438

American (AMR) AF: 0.744 AC: 11357 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2212 AN: 3470

East Asian (EAS) AF: 0.810 AC: 4182 AN: 5164

South Asian (SAS) AF: 0.672 AC: 3235 AN: 4812

European-Finnish (FIN) AF: 0.626 AC: 6617 AN: 10572

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

European-Non Finnish (NFE) AF: 0.579 AC: 39293 AN: 67906

Other (OTH) AF: 0.672 AC: 1418 AN: 2110

Alfa AF: 0.649 Hom.: 6629

Bravo AF: 0.659

Asia WGS AF: 0.733 AC: 2549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0060
DANN	Benign	0.48
PhyloP100		-2.0
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: rs647041; hg19: chr15-78880481;