chr15-78573551-G-A

Variant names:

• chr15-78573551-G-A
• rs6495306
• NM_000745.4:c.107-7260G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 37 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000745.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA5	NM_000745.4	MANE Select	c.107-7260G>A		intron	N/A	NP_000736.2
	CHRNA5	NM_001395171.1		c.107-7260G>A		intron	N/A	NP_001382100.1
	CHRNA5	NM_001395172.1		c.107-7260G>A		intron	N/A	NP_001382101.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA5	ENST00000299565.9	TSL:1 MANE Select	c.107-7260G>A		intron	N/A	ENSP00000299565.5
	CHRNA5	ENST00000559554.5	TSL:3	c.107-7260G>A		intron	N/A	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

African (AFR) AF: 0.695 AC: 28826 AN: 41468

American (AMR) AF: 0.745 AC: 11378 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2158 AN: 3468

East Asian (EAS) AF: 0.820 AC: 4243 AN: 5174

South Asian (SAS) AF: 0.671 AC: 3235 AN: 4824

European-Finnish (FIN) AF: 0.625 AC: 6603 AN: 10566

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39202 AN: 67964

Other (OTH) AF: 0.672 AC: 1416 AN: 2106

Alfa AF: 0.602 Hom.: 29665

Bravo AF: 0.655

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.2
DANN	Benign	0.88
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6495306; hg19: chr15-78865893;