dbSNP rs55853698: CHRNA5:c.-123T>G (chr15-78565597-T-G) – 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.-123T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 238,140 control chromosomes in the GnomAD database, including 10,646 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 0.25 ( 5904 hom., cov: 32)

Exomes 𝑓: 0.32 ( 4742 hom. )

Consequence

CHRNA5
NM_000745.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.123

Publications

48 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:

Genome browser will be placed here

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=-0.78).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA5	NM_000745.4 link	c.-123T>G		5_prime_UTR_variant	Exon 1 of 6	ENST00000299565.9	NP_000736.2	P30532Q6EWN4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9 link	c.-123T>G		5_prime_UTR_variant	Exon 1 of 6	1	NM_000745.4	ENSP00000299565.5		P30532
CHRNA5	ENST00000559554.5 link	c.-123T>G		5_prime_UTR_variant	Exon 1 of 6	3		ENSP00000453519.1		H0YM98

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37692

AN:

151938

Hom.:

5903

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0820

Gnomad AMI

AF:

0.406

Gnomad AMR

AF:

0.228

Gnomad ASJ

AF:

0.354

Gnomad EAS

AF:

0.0336

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.329

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.350

Gnomad OTH

AF:

0.275

GnomAD4 exome

AF:

0.324

AC:

27866

AN:

86092

Hom.:

4742

Cov.:

AF XY:

0.322

AC XY:

14664

AN XY:

45600

show subpopulations

African (AFR)

AF:

0.0770

AC:

143

AN:

1858

American (AMR)

AF:

0.217

AC:

467

AN:

2152

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

681

AN:

1996

East Asian (EAS)

AF:

0.0246

AC:

AN:

3692

South Asian (SAS)

AF:

0.216

AC:

227

AN:

1052

European-Finnish (FIN)

AF:

0.341

AC:

2395

AN:

7016

Middle Eastern (MID)

AF:

0.343

AC:

390

AN:

1136

European-Non Finnish (NFE)

AF:

0.354

AC:

22160

AN:

62512

Other (OTH)

AF:

0.280

AC:

1312

AN:

4678

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

890

1780

2670

3560

4450

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

364

728

1092

1456

1820

<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:

0.248

AC:

37703

AN:

152048

Hom.:

5904

Cov.:

AF XY:

0.245

AC XY:

18188

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0820

AC:

3401

AN:

41496

American (AMR)

AF:

0.228

AC:

3484

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.354

AC:

1227

AN:

3470

East Asian (EAS)

AF:

0.0339

AC:

175

AN:

5162

South Asian (SAS)

AF:

0.226

AC:

1092

AN:

4826

European-Finnish (FIN)

AF:

0.329

AC:

3473

AN:

10558

Middle Eastern (MID)

AF:

0.395

AC:

116

AN:

294

European-Non Finnish (NFE)

AF:

0.350

AC:

23789

AN:

67938

Other (OTH)

AF:

0.273

AC:

577

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1402

2805

4207

5610

7012

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

380

760

1140

1520

1900

<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:

0.242

Hom.:

1633

Bravo

AF:

0.232

Asia WGS

AF:

0.122

AC:

427

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

7.1

(source)

DANN

Benign

0.38

PhyloP100

-0.12

PromoterAI

0.060

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=298/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over