rs514743

chr15-78591885-T-Achr15-78591885-T-Cchr15-78591885-T-G

Variant summary

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

The NM_000745.4(CHRNA5):c.1246-1207T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 152,106 control chromosomes in the GnomAD database, including 36,753 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 0.69 (36753 hom., cov: 32)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA5	NM_000745.4	c.1246-1207T>A		intron_variant		ENST00000299565.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA5	ENST00000299565.9	c.1246-1207T>A		intron_variant		1	NM_000745.4	P1
CHRNA5	ENST00000394802.4	c.523-1207T>A		intron_variant		3
CHRNA5	ENST00000559554.5	c.459-1207T>A		intron_variant		3
CHRNA5	ENST00000559576.1	c.146-1207T>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.691 AC: 105030 AN: 151988 Hom.: 36700 Cov.: 32

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.691 AC: 105146 AN: 152106 Hom.: 36753 Cov.: 32 AF XY: 0.693 AC XY: 51568 AN XY: 74360

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.772

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.691

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.710

Alfa AF: 0.521 Hom.: 1344

Bravo AF: 0.705

Asia WGS AF: 0.753 AC: 2621 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	0.33
Dann	Benign	0.34

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: rs514743; hg19: chr15-78884227;