rs79109919

Variant names:

• chr15-78590479-T-A
• rs79109919
• NM_000745.4:c.1088T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000745.4(CHRNA5):​c.1088T>A​(p.Leu363Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00304 in 1,614,196 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (54 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (62 hom.)
• Consequence: CHRNA5 NM_000745.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 7.99
• Publications: 12 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]

ENSG00000261762 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014962435).
• BP6: Variant 15-78590479-T-A is Benign according to our data. Variant chr15-78590479-T-A is described in ClinVar as Benign. ClinVar VariationId is 714661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0525 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA5	NM_000745.4	MANE Select	c.1088T>A	p.Leu363Gln	missense	Exon 5 of 6	NP_000736.2
	CHRNA5	NM_001395171.1		c.1088T>A	p.Leu363Gln	missense	Exon 5 of 6	NP_001382100.1
	CHRNA5	NM_001395172.1		c.591+497T>A		intron	N/A	NP_001382101.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA5	ENST00000299565.9	TSL:1 MANE Select	c.1088T>A	p.Leu363Gln	missense	Exon 5 of 6	ENSP00000299565.5	P30532
	CHRNA5	ENST00000559576.1	TSL:3	c.116T>A	p.Leu39Gln	missense	Exon 1 of 2	ENSP00000452641.1	H0YK34
	CHRNA5	ENST00000913028.1		c.591+497T>A		intron	N/A	ENSP00000583087.1

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2387 AN: 152192 Hom.: 54 Cov.: 32

Gnomad AFR AF: 0.0543

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00416 AC: 1046 AN: 251252 AF XY: 0.00297

Gnomad AFR exome AF: 0.0538

Gnomad AMR exome AF: 0.00220

Gnomad ASJ exome AF: 0.00516

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000255

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00171 AC: 2503 AN: 1461886 Hom.: 62 Cov.: 31 AF XY: 0.00151 AC XY: 1096 AN XY: 727242

African (AFR) AF: 0.0564 AC: 1887 AN: 33480

American (AMR) AF: 0.00266 AC: 119 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00551 AC: 144 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5768

European-Non Finnish (NFE) AF: 0.0000908 AC: 101 AN: 1112010

Other (OTH) AF: 0.00368 AC: 222 AN: 60396

GnomAD4 genome AF: 0.0157 AC: 2398 AN: 152310 Hom.: 54 Cov.: 32 AF XY: 0.0151 AC XY: 1122 AN XY: 74486

African (AFR) AF: 0.0544 AC: 2261 AN: 41556

American (AMR) AF: 0.00490 AC: 75 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68032

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.00262 Hom.: 5

Bravo AF: 0.0175

ESP6500AA AF: 0.0519 AC: 228

ESP6500EA AF: 0.000582 AC: 5

ExAC AF: 0.00520 AC: 631

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.81	D
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		8.0
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.7	D
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.99	D
Vest4		0.87
MVP		0.91
MPC		0.82
ClinPred		0.024	T
GERP RS		4.9
PromoterAI		-0.0038	Neutral
Varity_R		0.74
gMVP		0.83
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs79109919; hg19: chr15-78882821;