dbSNP rs3749147: GPN1:p.Arg12Lys (chr2-27629051-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000264718.7(GPN1):c.35G>A(p.Arg12Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,613,938 control chromosomes in the GnomAD database, including 50,452 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3790 hom., cov: 32)

Exomes 𝑓: 0.25 ( 46662 hom. )

Consequence

GPN1
ENST00000264718.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.742

Publications

58 publications found

Variant links:

Genes affected

GPN1 (HGNC:17030): (GPN-loop GTPase 1) This gene encodes a guanosine triphosphatase enzyme. The encoded protein may play a role in DNA repair and may function in activation of transcription. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2009]

GPN1 links:

ENSG00000259080 (HGNC:):

ENSG00000259080 links:

CCDC121 (HGNC:25833): (coiled-coil domain containing 121)

CCDC121 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 (MetaRNN=0.0043020844).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPN1	NM_007266.4 link	c.-8G>A		5_prime_UTR_variant	Exon 1 of 14	ENST00000610189.2	NP_009197.3	Q9HCN4-1Q53RZ9
CCDC121	NM_024584.5 link	c.-220C>T		upstream_gene_variant		ENST00000324364.4	NP_078860.2	Q6ZUS5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPN1	ENST00000610189.2 link	c.-8G>A		5_prime_UTR_variant	Exon 1 of 14	1	NM_007266.4	ENSP00000476446.1		Q9HCN4-1
CCDC121	ENST00000324364.4 link	c.-220C>T		upstream_gene_variant		1	NM_024584.5	ENSP00000339087.2		Q6ZUS5-1

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30876

AN:

152098

Hom.:

3791

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0642

Gnomad AMI

AF:

0.193

Gnomad AMR

AF:

0.203

Gnomad ASJ

AF:

0.345

Gnomad EAS

AF:

0.307

Gnomad SAS

AF:

0.179

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.250

GnomAD2 exomes

AF:

0.229

AC:

57492

AN:

251142

AF XY:

0.234

show subpopulations

Gnomad AFR exome

AF:

0.0576

Gnomad AMR exome

AF:

0.139

Gnomad ASJ exome

AF:

0.345

Gnomad EAS exome

AF:

0.309

Gnomad FIN exome

AF:

0.254

Gnomad NFE exome

AF:

0.263

Gnomad OTH exome

AF:

0.257

GnomAD4 exome

AF:

0.247

AC:

361611

AN:

1461722

Hom.:

46662

Cov.:

AF XY:

0.247

AC XY:

179937

AN XY:

727168

show subpopulations

African (AFR)

AF:

0.0559

AC:

1871

AN:

33478

American (AMR)

AF:

0.144

AC:

6441

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

8938

AN:

26134

East Asian (EAS)

AF:

0.348

AC:

13826

AN:

39686

South Asian (SAS)

AF:

0.187

AC:

16138

AN:

86250

European-Finnish (FIN)

AF:

0.249

AC:

13279

AN:

53380

Middle Eastern (MID)

AF:

0.315

AC:

1815

AN:

5766

European-Non Finnish (NFE)

AF:

0.256

AC:

284142

AN:

1111922

Other (OTH)

AF:

0.251

AC:

15161

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

15635

31270

46905

62540

78175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9374

18748

28122

37496

46870

<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:

0.203

AC:

30872

AN:

152216

Hom.:

3790

Cov.:

AF XY:

0.203

AC XY:

15136

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0640

AC:

2660

AN:

41566

American (AMR)

AF:

0.203

AC:

3107

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.345

AC:

1199

AN:

3472

East Asian (EAS)

AF:

0.307

AC:

1586

AN:

5164

South Asian (SAS)

AF:

0.179

AC:

864

AN:

4822

European-Finnish (FIN)

AF:

0.258

AC:

2729

AN:

10594

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.264

AC:

17923

AN:

67990

Other (OTH)

AF:

0.252

AC:

531

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1191

2382

3572

4763

5954

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

332

664

996

1328

1660

<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:

0.244

Hom.:

17242

Bravo

AF:

0.192

TwinsUK

AF:

0.251

AC:

931

ALSPAC

AF:

0.249

AC:

961

ESP6500AA

AF:

0.0663

AC:

292

ESP6500EA

AF:

0.265

AC:

2283

ExAC

AF:

0.225

AC:

27292

Asia WGS

AF:

0.202

AC:

703

AN:

3478

EpiCase

AF:

0.287

EpiControl

AF:

0.287

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.91

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.41

T;.

MetaRNN

Benign

0.0043

T;T

MetaSVM

Benign

-0.96

PhyloP100

0.74

PrimateAI

Uncertain

0.61

PROVEAN

Benign

0.040

.;N

REVEL

Benign

0.031

Sift

Benign

0.63

.;T

Sift4G

Benign

0.90

T;T

Vest4

0.11

MPC

0.21

ClinPred

0.0038

GERP RS

1.9

PromoterAI

0.078

Neutral

(source)

gMVP

0.49

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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