Genetic Variant CHRNA5:c.-166T>A (chr15-78565554-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000745.4(CHRNA5):c.-166T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 215,114 control chromosomes in the GnomAD database, including 9,738 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 0.29 ( 7122 hom., cov: 33)

Exomes 𝑓: 0.27 ( 2616 hom. )

Consequence

CHRNA5
NM_000745.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.176

Publications

32 publications found

Variant links:

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]

CHRNA5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.476 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CHRNA5	NM_000745.4	MANE Select	c.-166T>A	5_prime_UTR	Exon 1 of 6	NP_000736.2
CHRNA5	NM_001395171.1		c.-166T>A	5_prime_UTR	Exon 1 of 6	NP_001382100.1
CHRNA5	NM_001395172.1		c.-166T>A	5_prime_UTR	Exon 1 of 6	NP_001382101.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRNA5	ENST00000299565.9	TSL:1 MANE Select	c.-166T>A	5_prime_UTR	Exon 1 of 6	ENSP00000299565.5	P30532
CHRNA5	ENST00000913028.1		c.-166T>A	5_prime_UTR	Exon 1 of 6	ENSP00000583087.1
CHRNA5	ENST00000559554.5	TSL:3	c.-166T>A	upstream_gene	N/A	ENSP00000453519.1	H0YM98

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43809

AN:

151910

Hom.:

7097

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.484

Gnomad SAS

AF:

0.481

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.327

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.299

GnomAD4 exome

AF:

0.273

AC:

17229

AN:

63098

Hom.:

2616

Cov.:

AF XY:

0.274

AC XY:

9369

AN XY:

34222

show subpopulations

African (AFR)

AF:

0.277

AC:

397

AN:

1432

American (AMR)

AF:

0.543

AC:

1068

AN:

1966

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

496

AN:

1842

East Asian (EAS)

AF:

0.520

AC:

1730

AN:

3330

South Asian (SAS)

AF:

0.505

AC:

311

AN:

616

European-Finnish (FIN)

AF:

0.301

AC:

1961

AN:

6516

Middle Eastern (MID)

AF:

0.289

AC:

133

AN:

460

European-Non Finnish (NFE)

AF:

0.231

AC:

9952

AN:

43078

Other (OTH)

AF:

0.306

AC:

1181

AN:

3858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

589

1178

1766

2355

2944

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.289

AC:

43860

AN:

152016

Hom.:

7122

Cov.:

AF XY:

0.299

AC XY:

22184

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.269

AC:

11156

AN:

41480

American (AMR)

AF:

0.485

AC:

7414

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

847

AN:

3468

East Asian (EAS)

AF:

0.484

AC:

2487

AN:

5140

South Asian (SAS)

AF:

0.481

AC:

2321

AN:

4822

European-Finnish (FIN)

AF:

0.308

AC:

3257

AN:

10568

Middle Eastern (MID)

AF:

0.324

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.228

AC:

15496

AN:

67938

Other (OTH)

AF:

0.307

AC:

650

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1573

3146

4720

6293

7866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.258

Hom.:

688

Bravo

AF:

0.300

Asia WGS

AF:

0.489

AC:

1694

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.3

(source)

DANN

Benign

0.60

PhyloP100

-0.18

PromoterAI

-0.045

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over