15-78588139-T-C

Position:

• chr15-78588139-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• 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/exons	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.304-175T>C		intron_variant		ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9	c.304-175T>C		intron_variant		1	NM_000745.4	ENSP00000299565	P1
CHRNA5	ENST00000394802.4	c.119-175T>C		intron_variant		3		ENSP00000378281
CHRNA5	ENST00000559554.5	c.304-175T>C		intron_variant		3		ENSP00000453519

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

Gnomad4 AFR AF: 0.707

Gnomad4 AMR AF: 0.744

Gnomad4 ASJ AF: 0.637

Gnomad4 EAS AF: 0.810

Gnomad4 SAS AF: 0.672

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.672

Alfa AF: 0.641 Hom.: 5509

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

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: rs647041; hg19: chr15-78880481;