15-78577588-C-T

Position:

• chr15-78577588-C-T

Variant summary

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

The NM_000745.4(CHRNA5):​c.107-3223C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 151,912 control chromosomes in the GnomAD database, including 31,239 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 (31239 hom., cov: 31)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.107-3223C>T		intron_variant		ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9	c.107-3223C>T		intron_variant		1	NM_000745.4	ENSP00000299565	P1
CHRNA5	ENST00000559554.5	c.107-3223C>T		intron_variant		3		ENSP00000453519

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96873 AN: 151792 Hom.: 31194 Cov.: 31

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.668

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

GnomAD4 genome AF: 0.638 AC: 96981 AN: 151912 Hom.: 31239 Cov.: 31 AF XY: 0.642 AC XY: 47632 AN XY: 74240

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.762

Gnomad4 SAS AF: 0.687

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.672

Alfa AF: 0.619 Hom.: 3619

Bravo AF: 0.644

Asia WGS AF: 0.719 AC: 2501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.7
DANN	Benign	0.37

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: rs495956; hg19: chr15-78869930;