dbSNP rs534031880: CHRNA5:p.Gln18Gln (chr15-78565773-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000745.4(CHRNA5):c.54G>A(p.Gln18Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000314 in 1,218,754 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00052 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00029 ( 2 hom. )

Consequence

CHRNA5
NM_000745.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.19

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 15-78565773-G-A is Benign according to our data. Variant chr15-78565773-G-A is described in ClinVar as Benign. ClinVar VariationId is 732206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.19 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

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.54G>A	p.Gln18Gln	synonymous	Exon 1 of 6	NP_000736.2
CHRNA5	NM_001395171.1		c.54G>A	p.Gln18Gln	synonymous	Exon 1 of 6	NP_001382100.1
CHRNA5	NM_001395172.1		c.54G>A	p.Gln18Gln	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.54G>A	p.Gln18Gln	synonymous	Exon 1 of 6	ENSP00000299565.5	P30532
CHRNA5	ENST00000913028.1		c.54G>A	p.Gln18Gln	synonymous	Exon 1 of 6	ENSP00000583087.1
CHRNA5	ENST00000559554.5	TSL:3	c.54G>A	p.Gln18Gln	synonymous	Exon 1 of 6	ENSP00000453519.1	H0YM98

Frequencies

GnomAD3 genomes

AF:

0.000523

AC:

AN:

151166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000659

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0152

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000286

AC:

305

AN:

1067478

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

142

AN XY:

504046

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22372

American (AMR)

AF:

0.00

AC:

AN:

7992

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13722

East Asian (EAS)

AF:

0.0105

AC:

269

AN:

25724

South Asian (SAS)

AF:

0.000206

AC:

AN:

19400

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20816

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2894

European-Non Finnish (NFE)

AF:

0.00000110

AC:

AN:

911872

Other (OTH)

AF:

0.000726

AC:

AN:

42686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

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:

0.000516

AC:

AN:

151276

Hom.:

Cov.:

AF XY:

0.000541

AC XY:

AN XY:

73934

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41372

American (AMR)

AF:

0.0000658

AC:

AN:

15200

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0151

AC:

AN:

5104

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10246

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67762

Other (OTH)

AF:

0.00

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000654

Asia WGS

AF:

0.00261

AC:

AN:

3460

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

-0.76

CADD

Benign

9.8

(source)

DANN

Benign

0.92

PhyloP100

1.2

PromoterAI

0.038

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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

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