dbSNP rs17408276: CHRNA5:c.414-529T>C (chr15-78589276-T-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.414-529T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,332 control chromosomes in the GnomAD database, including 6,721 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 0.28 ( 6713 hom., cov: 32)

Exomes 𝑓: 0.28 ( 8 hom. )

Consequence

CHRNA5
NM_000745.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.147

Publications

26 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:

ENSG00000261762 (HGNC:):

ENSG00000261762 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=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA5	NM_000745.4 link	c.414-529T>C		intron_variant	Intron 4 of 5	ENST00000299565.9	NP_000736.2	P30532Q6EWN4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHRNA5	ENST00000299565.9 link	c.414-529T>C	intron_variant	Intron 4 of 5	1	NM_000745.4	ENSP00000299565.5	P30532
ENSG00000261762	ENST00000567141.1 link	n.2001A>G	non_coding_transcript_exon_variant	Exon 1 of 1	6
CHRNA5	ENST00000394802.4 link	c.228-529T>C	intron_variant	Intron 3 of 4	3		ENSP00000378281.4	H7BYM0
CHRNA5	ENST00000559554.5 link	c.414-529T>C	intron_variant	Intron 4 of 5	3		ENSP00000453519.1	H0YM98

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

41899

AN:

152066

Hom.:

6717

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.413

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.303

Gnomad FIN

AF:

0.350

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.371

Gnomad OTH

AF:

0.276

GnomAD4 exome

AF:

0.277

AC:

AN:

148

Hom.:

Cov.:

AF XY:

0.244

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.125

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.200

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.327

AC:

AN:

104

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.275

AC:

41891

AN:

152184

Hom.:

6713

Cov.:

AF XY:

0.275

AC XY:

20434

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.122

AC:

5084

AN:

41538

American (AMR)

AF:

0.215

AC:

3289

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1202

AN:

3464

East Asian (EAS)

AF:

0.182

AC:

944

AN:

5188

South Asian (SAS)

AF:

0.302

AC:

1455

AN:

4822

European-Finnish (FIN)

AF:

0.350

AC:

3700

AN:

10568

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.371

AC:

25205

AN:

67990

Other (OTH)

AF:

0.273

AC:

577

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1497

2994

4492

5989

7486

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:

0.292

Hom.:

3177

Bravo

AF:

0.258

Asia WGS

AF:

0.237

AC:

822

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.7

(source)

DANN

Benign

0.36

PhyloP100

0.15

Mutation Taster

=100/0

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

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