Variant 6-32182309-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP3BP4_StrongBP6BS2

The NM_001136.5(AGER):c.902G>C(p.Cys301Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00106 in 1,612,668 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 8 hom. )

Consequence

AGER
NM_001136.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 3.99

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.

PP3

Multiple lines of computational evidence support a deleterious effect 7: AlphaMissense, BayesDel_noAF, Cadd, Eigen, MutationAssessor, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, M_CAP, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.02679661).

BP6

Variant 6-32182309-C-G is Benign according to our data. Variant chr6-32182309-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 710266.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGER	NM_001136.5 linkuse as main transcript	c.902G>C	p.Cys301Ser	missense_variant	8/11	ENST00000375076.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGER	ENST00000375076.9 linkuse as main transcript	c.902G>C	p.Cys301Ser	missense_variant	8/11	1	NM_001136.5	P1	Q15109-1

Frequencies

GnomAD3 genomes

AF:

0.00151

AC:

229

AN:

151926

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00531

Gnomad ASJ

AF:

0.0283

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000530

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00215

AC:

530

AN:

246258

Hom.:

AF XY:

0.00208

AC XY:

279

AN XY:

134250

show subpopulations

Gnomad AFR exome

AF:

0.000199

Gnomad AMR exome

AF:

0.00351

Gnomad ASJ exome

AF:

0.0307

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000988

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000669

Gnomad OTH exome

AF:

0.00379

GnomAD4 exome

AF:

0.00101

AC:

1474

AN:

1460624

Hom.:

Cov.:

AF XY:

0.00100

AC XY:

727

AN XY:

726626

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00349

Gnomad4 ASJ exome

AF:

0.0305

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000305

Gnomad4 OTH exome

AF:

0.00277

GnomAD4 genome

AF:

0.00151

AC:

229

AN:

152044

Hom.:

Cov.:

AF XY:

0.00182

AC XY:

135

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00530

Gnomad4 ASJ

AF:

0.0283

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000530

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00246

Hom.:

Bravo

AF:

0.00165

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000332

AC:

ESP6500EA

AF:

0.000554

AC:

ExAC

AF:

0.00147

AC:

173

EpiCase

AF:

0.000709

EpiControl

AF:

0.00107

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Uncertain

0.030

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

.;.;.;.;T;T

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

D;D;D;.;D;.

M_CAP

Benign

0.082

MetaRNN

Benign

0.027

T;T;T;T;T;T

MetaSVM

Uncertain

0.27

MutationAssessor

Pathogenic

4.2

H;.;.;.;H;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-6.3

D;D;.;.;D;.

REVEL

Pathogenic

0.67

Sift

Uncertain

0.0010

D;D;.;.;D;.

Sift4G

Pathogenic

0.0

D;D;D;T;D;D

Polyphen

1.0

D;.;.;D;D;.

Vest4

0.95

MutPred

0.79

Gain of disorder (P = 0.0304);.;.;.;Gain of disorder (P = 0.0304);.;

MVP

0.90

MPC

0.73

ClinPred

0.18

GERP RS

5.7

Varity_R

0.70

gMVP

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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