Genetic Variant NM_000745.4:c.80C>T (chr15-78565799-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000745.4(CHRNA5):c.80C>T(p.Ala27Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000876 in 1,222,062 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000085 ( 1 hom. )

Consequence

CHRNA5
NM_000745.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0650

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0490402).

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	HGVSp	Effect	Exon Rank	Protein
CHRNA5	NM_000745.4	MANE Select	c.80C>T	p.Ala27Val	missense	Exon 1 of 6	NP_000736.2
CHRNA5	NM_001395171.1		c.80C>T	p.Ala27Val	missense	Exon 1 of 6	NP_001382100.1
CHRNA5	NM_001395172.1		c.80C>T	p.Ala27Val	missense	Exon 1 of 6	NP_001382101.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHRNA5	ENST00000299565.9	TSL:1 MANE Select	c.80C>T	p.Ala27Val	missense	Exon 1 of 6	ENSP00000299565.5	P30532
CHRNA5	ENST00000913028.1		c.80C>T	p.Ala27Val	missense	Exon 1 of 6	ENSP00000583087.1
CHRNA5	ENST00000559554.5	TSL:3	c.80C>T	p.Ala27Val	missense	Exon 1 of 6	ENSP00000453519.1	H0YM98

Frequencies

GnomAD3 genomes

AF:

0.000113

AC:

AN:

150868

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000589

Gnomad SAS

AF:

0.000831

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00649

Gnomad NFE

AF:

0.0000444

Gnomad OTH

AF:

0.00145

GnomAD2 exomes

AF:

0.00

AC:

AN:

334

AF XY:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000850

AC:

AN:

1071086

Hom.:

Cov.:

AF XY:

0.0000909

AC XY:

AN XY:

505782

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22512

American (AMR)

AF:

0.00

AC:

AN:

8110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13922

East Asian (EAS)

AF:

0.0000384

AC:

AN:

26008

South Asian (SAS)

AF:

0.000463

AC:

AN:

19422

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20890

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

2880

European-Non Finnish (NFE)

AF:

0.0000744

AC:

AN:

914374

Other (OTH)

AF:

0.000279

AC:

AN:

42968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.000106

AC:

AN:

150976

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

73746

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41276

American (AMR)

AF:

0.0000657

AC:

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.000591

AC:

AN:

5076

South Asian (SAS)

AF:

0.000624

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10300

Middle Eastern (MID)

AF:

0.00699

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0000444

AC:

AN:

67550

Other (OTH)

AF:

0.00143

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000945

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.025

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.29

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.065

PrimateAI

Uncertain

0.71

PROVEAN

Benign

0.12

REVEL

Benign

0.10

Sift

Benign

0.37

Sift4G

Benign

0.61

Polyphen

0.076

Vest4

0.12

MutPred

0.41

Loss of disorder (P = 0.0501)

MVP

0.46

MPC

0.21

ClinPred

0.095

GERP RS

-0.019

PromoterAI

-0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.025

gMVP

0.21

Mutation Taster

=94/6

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over