rs6495306

Positions:

• chr15-78573551-G-A
• chr15-78573551-G-C
• chr15-78573551-G-T

Variant summary

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

The NM_000745.4(CHRNA5):​c.107-7260G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,054 control chromosomes in the GnomAD database, including 31,900 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 (31900 hom., cov: 32)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52

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=-0.83).
• 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	Protein	UniProt
CHRNA5	NM_000745.4	c.107-7260G>A		intron_variant		ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9	c.107-7260G>A		intron_variant		1	NM_000745.4	ENSP00000299565.5
CHRNA5	ENST00000559554.5	c.107-7260G>A		intron_variant		3		ENSP00000453519.1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97693 AN: 151936 Hom.: 31850 Cov.: 32

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.625

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: 0.643 AC: 97805 AN: 152054 Hom.: 31900 Cov.: 32 AF XY: 0.648 AC XY: 48142 AN XY: 74330

Gnomad4 AFR AF: 0.695

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.672

Alfa AF: 0.591 Hom.: 21146

Bravo AF: 0.655

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.2
DANN	Benign	0.88

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: rs6495306; hg19: chr15-78865893;