Variant rs2070600 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

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). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGER	NM_001136.5 linkuse as main transcript	c.244G>A	p.Gly82Ser	missense_variant	3/11	ENST00000375076.9	NP_001127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGER	ENST00000375076.9 linkuse as main transcript	c.244G>A	p.Gly82Ser	missense_variant	3/11	1	NM_001136.5	ENSP00000364217	P1	Q15109-1

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

GnomAD3 exomes

AF:

0.0532

AC:

13091

AN:

245924

Hom.:

666

AF XY:

0.0540

AC XY:

7250

AN XY:

134274

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 SAS exome

AF:

0.0656

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

Gnomad4 AFR exome

AF:

0.00765

Gnomad4 AMR exome

AF:

0.00738

Gnomad4 ASJ exome

AF:

0.00983

Gnomad4 EAS exome

AF:

0.174

Gnomad4 SAS exome

AF:

0.0622

Gnomad4 FIN exome

AF:

0.0647

Gnomad4 NFE exome

AF:

0.0583

Gnomad4 OTH exome

AF:

0.0539

GnomAD4 genome

AF:

0.0387

AC:

5895

AN:

152250

Hom.:

234

Cov.:

AF XY:

0.0403

AC XY:

3002

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00987

Gnomad4 AMR

AF:

0.00980

Gnomad4 ASJ

AF:

0.00980

Gnomad4 EAS

AF:

0.206

Gnomad4 SAS

AF:

0.0611

Gnomad4 FIN

AF:

0.0702

Gnomad4 NFE

AF:

0.0456

Gnomad4 OTH

AF:

0.0241

Alfa

AF:

0.0477

Hom.:

565

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

COPD, severe early onset

Uncertain:1

Uncertain significance, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Aug 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

.;.;.;.;T;T;.;.;.

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.84

T;T;T;T;T;T;T;T;T

MetaRNN

Benign

0.0017

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.8

.;M;M;M;.;M;.;.;.

MutationTaster

Benign

0.0020

P;P;P;P;P;P;P;P;P

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.9

N;N;N;.;.;N;N;N;D

REVEL

Benign

0.16

Sift

Benign

0.51

T;T;T;.;.;T;T;T;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;.;.;D

Polyphen

1.0

D;D;.;.;.;D;.;.;.

Vest4

0.69

MPC

0.65

ClinPred

0.040

GERP RS

5.8

Varity_R

0.20

gMVP

0.43

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over