rs621849

Variant names:

• chr15-78580519-G-A
• rs621849
• NM_000745.4:c.107-292G>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.107-292G>A 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 151,956 control chromosomes in the GnomAD database, including 28,150 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 (28150 hom., cov: 32)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.933
• Publications: 30 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=-0.97).
• 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 rank	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.107-292G>A		intron_variant	Intron 1 of 5	ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9	c.107-292G>A		intron_variant	Intron 1 of 5	1	NM_000745.4	ENSP00000299565.5
CHRNA5	ENST00000559554.5	c.107-292G>A		intron_variant	Intron 1 of 5	3		ENSP00000453519.1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91871 AN: 151838 Hom.: 28109 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.626

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: 91975 AN: 151956 Hom.: 28150 Cov.: 32 AF XY: 0.610 AC XY: 45300 AN XY: 74278

African (AFR) AF: 0.575 AC: 23831 AN: 41438

American (AMR) AF: 0.730 AC: 11146 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2119 AN: 3472

East Asian (EAS) AF: 0.754 AC: 3897 AN: 5170

South Asian (SAS) AF: 0.667 AC: 3213 AN: 4820

European-Finnish (FIN) AF: 0.626 AC: 6597 AN: 10534

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39084 AN: 67946

Other (OTH) AF: 0.641 AC: 1353 AN: 2112

Alfa AF: 0.598 Hom.: 15622

Bravo AF: 0.612

Asia WGS AF: 0.702 AC: 2441 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	0.11
DANN	Benign	0.47
PhyloP100		-0.93
PromoterAI		-0.014	Neutral
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: rs621849; hg19: chr15-78872861;