Genetic Variant CHRNA5:p.Gly31Gly (chr15-78565812-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_000745.4(CHRNA5):c.93C>T(p.Gly31Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,220,808 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00076 ( 1 hom., cov: 31)

Exomes 𝑓: 0.000072 ( 0 hom. )

Consequence

CHRNA5
NM_000745.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.343

Publications

1 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 15-78565812-C-T is Benign according to our data. Variant chr15-78565812-C-T is described in ClinVar as Benign. ClinVar VariationId is 752583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.343 with no splicing effect.

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.93C>T	p.Gly31Gly	synonymous	Exon 1 of 6	NP_000736.2
CHRNA5	NM_001395171.1		c.93C>T	p.Gly31Gly	synonymous	Exon 1 of 6	NP_001382100.1
CHRNA5	NM_001395172.1		c.93C>T	p.Gly31Gly	synonymous	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.93C>T	p.Gly31Gly	synonymous	Exon 1 of 6	ENSP00000299565.5	P30532
CHRNA5	ENST00000913028.1		c.93C>T	p.Gly31Gly	synonymous	Exon 1 of 6	ENSP00000583087.1
CHRNA5	ENST00000559554.5	TSL:3	c.93C>T	p.Gly31Gly	synonymous	Exon 1 of 6	ENSP00000453519.1	H0YM98

Frequencies

GnomAD3 genomes

AF:

0.000754

AC:

113

AN:

149934

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00262

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000264

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000975

GnomAD4 exome

AF:

0.0000719

AC:

AN:

1070766

Hom.:

Cov.:

AF XY:

0.0000712

AC XY:

AN XY:

505670

show subpopulations

African (AFR)

AF:

0.00267

AC:

AN:

22496

American (AMR)

AF:

0.000370

AC:

AN:

8106

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13936

East Asian (EAS)

AF:

0.00

AC:

AN:

26012

South Asian (SAS)

AF:

0.00

AC:

AN:

19424

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20862

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2880

European-Non Finnish (NFE)

AF:

0.00000438

AC:

AN:

914066

Other (OTH)

AF:

0.000233

AC:

AN:

42984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000760

AC:

114

AN:

150042

Hom.:

Cov.:

AF XY:

0.000764

AC XY:

AN XY:

73254

show subpopulations

African (AFR)

AF:

0.00263

AC:

108

AN:

40996

American (AMR)

AF:

0.000264

AC:

AN:

15144

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3444

East Asian (EAS)

AF:

0.00

AC:

AN:

4922

South Asian (SAS)

AF:

0.00

AC:

AN:

4740

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67256

Other (OTH)

AF:

0.000965

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.000712

Hom.:

Bravo

AF:

0.000839

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

0.34

PromoterAI

-0.037

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

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