Genetic Variant CHRNA5:c.304-79G>C (chr15-78588235-G-C) – 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.304-79G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0381 in 688,938 control chromosomes in the GnomAD database, including 615 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 0.031 ( 109 hom., cov: 32)

Exomes 𝑓: 0.040 ( 506 hom. )

Consequence

CHRNA5
NM_000745.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.00

Publications

13 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=-0.91).

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0517 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.304-79G>C	intron	N/A	NP_000736.2
CHRNA5	NM_001395171.1		c.304-79G>C	intron	N/A	NP_001382100.1
CHRNA5	NM_001395172.1		c.304-79G>C	intron	N/A	NP_001382101.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CHRNA5	ENST00000299565.9	TSL:1 MANE Select	c.304-79G>C	intron	N/A	ENSP00000299565.5
CHRNA5	ENST00000394802.4	TSL:3	c.118-79G>C	intron	N/A	ENSP00000378281.4
CHRNA5	ENST00000559554.5	TSL:3	c.304-79G>C	intron	N/A	ENSP00000453519.1

Frequencies

GnomAD3 genomes

AF:

0.0307

AC:

4674

AN:

152036

Hom.:

109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00930

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0238

Gnomad ASJ

AF:

0.0208

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0153

Gnomad FIN

AF:

0.0264

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0504

Gnomad OTH

AF:

0.0287

GnomAD4 exome

AF:

0.0401

AC:

21544

AN:

536784

Hom.:

506

AF XY:

0.0392

AC XY:

11067

AN XY:

282632

show subpopulations

African (AFR)

AF:

0.00965

AC:

128

AN:

13268

American (AMR)

AF:

0.0188

AC:

409

AN:

21720

Ashkenazi Jewish (ASJ)

AF:

0.0164

AC:

234

AN:

14252

East Asian (EAS)

AF:

0.0000641

AC:

AN:

31182

South Asian (SAS)

AF:

0.0156

AC:

624

AN:

40106

European-Finnish (FIN)

AF:

0.0285

AC:

1218

AN:

42726

Middle Eastern (MID)

AF:

0.0292

AC:

106

AN:

3628

European-Non Finnish (NFE)

AF:

0.0523

AC:

17912

AN:

342382

Other (OTH)

AF:

0.0331

AC:

911

AN:

27520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

983

1965

2948

3930

4913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

316

632

948

1264

1580

<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:

0.0307

AC:

4675

AN:

152154

Hom.:

109

Cov.:

AF XY:

0.0292

AC XY:

2173

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.00930

AC:

386

AN:

41522

American (AMR)

AF:

0.0237

AC:

363

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0208

AC:

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.0154

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0264

AC:

279

AN:

10562

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0504

AC:

3425

AN:

67990

Other (OTH)

AF:

0.0284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

232

463

695

926

1158

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0179

Hom.:

Bravo

AF:

0.0297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.59

(source)

DANN

Benign

0.59

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism

(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