Genetic Variant NM_001136.5:c.244G>A (chr6-32183666-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3BA1

The NM_001136.5(AGER):c.244G>A(p.Gly82Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0561 in 1,613,010 control chromosomes in the GnomAD database, including 3,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.039 ( 234 hom., cov: 33)

Exomes 𝑓: 0.058 ( 3131 hom. )

Consequence

AGER
NM_001136.5 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 2.46

Publications

465 publications found

Variant links:

Genes affected

AGER (HGNC:320): (advanced glycosylation end-product specific receptor) The advanced glycosylation end product (AGE) receptor encoded by this gene is a member of the immunoglobulin superfamily of cell surface receptors. It is a multiligand receptor, and besides AGE, interacts with other molecules implicated in homeostasis, development, and inflammation, and certain diseases, such as diabetes and Alzheimer's disease. Many alternatively spliced transcript variants encoding different isoforms, as well as non-protein-coding variants, have been described for this gene (PMID:18089847). [provided by RefSeq, May 2011]

AGER links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AGER	NM_001136.5	MANE Select	c.244G>A	p.Gly82Ser	missense	Exon 3 of 11	NP_001127.1
AGER	NM_001206929.2		c.244G>A	p.Gly82Ser	missense	Exon 3 of 11	NP_001193858.1
AGER	NM_001206932.2		c.202G>A	p.Gly68Ser	missense	Exon 3 of 11	NP_001193861.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AGER	ENST00000375076.9	TSL:1 MANE Select	c.244G>A	p.Gly82Ser	missense	Exon 3 of 11	ENSP00000364217.4
AGER	ENST00000375069.7	TSL:1	c.244G>A	p.Gly82Ser	missense	Exon 3 of 11	ENSP00000364210.4
AGER	ENST00000438221.6	TSL:1	c.244G>A	p.Gly82Ser	missense	Exon 3 of 10	ENSP00000387887.2

Frequencies

GnomAD3 genomes

AF:

0.0388

AC:

5905

AN:

152132

Hom.:

234

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00990

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.00981

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.207

Gnomad SAS

AF:

0.0614

Gnomad FIN

AF:

0.0702

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0456

Gnomad OTH

AF:

0.0239

GnomAD2 exomes

AF:

0.0532

AC:

13091

AN:

245924

AF XY:

0.0540

show subpopulations

Gnomad AFR exome

AF:

0.00921

Gnomad AMR exome

AF:

0.00676

Gnomad ASJ exome

AF:

0.0107

Gnomad EAS exome

AF:

0.207

Gnomad FIN exome

AF:

0.0686

Gnomad NFE exome

AF:

0.0463

Gnomad OTH exome

AF:

0.0409

GnomAD4 exome

AF:

0.0580

AC:

84662

AN:

1460760

Hom.:

3131

Cov.:

AF XY:

0.0575

AC XY:

41809

AN XY:

726696

show subpopulations

African (AFR)

AF:

0.00765

AC:

256

AN:

33480

American (AMR)

AF:

0.00738

AC:

330

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00983

AC:

257

AN:

26136

East Asian (EAS)

AF:

0.174

AC:

6889

AN:

39700

South Asian (SAS)

AF:

0.0622

AC:

5368

AN:

86258

European-Finnish (FIN)

AF:

0.0647

AC:

3382

AN:

52308

Middle Eastern (MID)

AF:

0.0134

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0583

AC:

64846

AN:

1112002

Other (OTH)

AF:

0.0539

AC:

3257

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

5488

10977

16465

21954

27442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2624

5248

7872

10496

13120

<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:

0.0387

AC:

5895

AN:

152250

Hom.:

234

Cov.:

AF XY:

0.0403

AC XY:

3002

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.00987

AC:

410

AN:

41540

American (AMR)

AF:

0.00980

AC:

150

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00980

AC:

AN:

3468

East Asian (EAS)

AF:

0.206

AC:

1068

AN:

5184

South Asian (SAS)

AF:

0.0611

AC:

295

AN:

4830

European-Finnish (FIN)

AF:

0.0702

AC:

744

AN:

10604

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0456

AC:

3102

AN:

67998

Other (OTH)

AF:

0.0241

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

281

563

844

1126

1407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<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:

0.0435

Hom.:

735

Bravo

AF:

0.0339

TwinsUK

AF:

0.0655

AC:

243

ALSPAC

AF:

0.0804

AC:

310

ESP6500AA

AF:

0.0156

AC:

ESP6500EA

AF:

0.0456

AC:

247

ExAC

AF:

0.0530

AC:

6195

Asia WGS

AF:

0.104

AC:

361

AN:

3478

EpiCase

AF:

0.0405

EpiControl

AF:

0.0414

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

COPD, severe early onset (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.8

PhyloP100

2.5

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.9

REVEL

Benign

0.16

Sift

Benign

0.51

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.69

MPC

0.65

ClinPred

0.040

GERP RS

5.8

Varity_R

0.20

gMVP

0.43

Mutation Taster

=87/13

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.73

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.73

Position offset: -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