15-78573083-T-C

Variant names:

• chr15-78573083-T-C
• rs588765
• NM_000745.4:c.106+7258T>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.106+7258T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 152,112 control chromosomes in the GnomAD database, including 32,078 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 0.64 (32078 hom., cov: 32)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238
• Publications: 112 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=-0.98).
• 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.106+7258T>C		intron_variant	Intron 1 of 5	ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9	c.106+7258T>C		intron_variant	Intron 1 of 5	1	NM_000745.4	ENSP00000299565.5
CHRNA5	ENST00000559554.5	c.106+7258T>C		intron_variant	Intron 1 of 5	3		ENSP00000453519.1

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97966 AN: 151994 Hom.: 32025 Cov.: 32

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.668

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

GnomAD4 genome AF: 0.645 AC: 98081 AN: 152112 Hom.: 32078 Cov.: 32 AF XY: 0.649 AC XY: 48284 AN XY: 74362

African (AFR) AF: 0.700 AC: 29057 AN: 41486

American (AMR) AF: 0.745 AC: 11382 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 2167 AN: 3466

East Asian (EAS) AF: 0.821 AC: 4248 AN: 5176

South Asian (SAS) AF: 0.670 AC: 3234 AN: 4824

European-Finnish (FIN) AF: 0.626 AC: 6618 AN: 10580

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

European-Non Finnish (NFE) AF: 0.577 AC: 39209 AN: 67978

Other (OTH) AF: 0.673 AC: 1422 AN: 2114

Alfa AF: 0.613 Hom.: 50046

Bravo AF: 0.657

Asia WGS AF: 0.735 AC: 2556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.7
DANN	Benign	0.54
PhyloP100		-0.24
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: rs588765; hg19: chr15-78865425;