rs680244

Positions:

• chr15-78578946-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.107-1865T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 152,022 control chromosomes in the GnomAD database, including 28,141 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 0.61 (28141 hom., cov: 32)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.107-1865T>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.107-1865T>C		intron_variant		1	NM_000745.4	ENSP00000299565	P1
CHRNA5	ENST00000559554.5	c.107-1865T>C		intron_variant		3		ENSP00000453519

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91864 AN: 151902 Hom.: 28094 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.605 AC: 91979 AN: 152022 Hom.: 28141 Cov.: 32 AF XY: 0.610 AC XY: 45303 AN XY: 74302

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.753

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.641

Alfa AF: 0.589 Hom.: 54442

Bravo AF: 0.612

Asia WGS AF: 0.701 AC: 2439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.14
DANN	Benign	0.58

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: rs680244; hg19: chr15-78871288;