Genetic Variant AGER:p.Pro291Leu (chr6-32181442-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_172197.3(AGER):c.872C>T(p.Pro291Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,613,364 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 11 hom. )

Consequence

AGER
NM_172197.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.44

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054189563).

BP6

Variant 6-32181442-G-A is Benign according to our data. Variant chr6-32181442-G-A is described in ClinVar as [Benign]. Clinvar id is 735622.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGER	NM_001136.5 link	c.1027C>T	p.Leu343Leu	synonymous_variant	Exon 10 of 11	ENST00000375076.9	NP_001127.1	Q15109-1A0A1U9X785B4DNX3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGER	ENST00000375076.9 link	c.1027C>T	p.Leu343Leu	synonymous_variant	Exon 10 of 11	1	NM_001136.5	ENSP00000364217.4		Q15109-1

Frequencies

GnomAD3 genomes

AF:

0.00112

AC:

171

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.00637

Gnomad SAS

AF:

0.00683

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000809

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00202

AC:

499

AN:

247318

Hom.:

AF XY:

0.00224

AC XY:

302

AN XY:

134544

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000348

Gnomad ASJ exome

AF:

0.00784

Gnomad EAS exome

AF:

0.00503

Gnomad SAS exome

AF:

0.00583

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.00297

GnomAD4 exome

AF:

0.00121

AC:

1768

AN:

1461062

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

1027

AN XY:

726816

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000515

Gnomad4 ASJ exome

AF:

0.00866

Gnomad4 EAS exome

AF:

0.00282

Gnomad4 SAS exome

AF:

0.00645

Gnomad4 FIN exome

AF:

0.0000758

Gnomad4 NFE exome

AF:

0.000594

Gnomad4 OTH exome

AF:

0.00222

GnomAD4 genome

AF:

0.00112

AC:

171

AN:

152302

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00865

Gnomad4 EAS

AF:

0.00638

Gnomad4 SAS

AF:

0.00683

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000809

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00153

Hom.:

Bravo

AF:

0.00104

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000738

AC:

ExAC

AF:

0.00219

AC:

264

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.00174

EpiControl

AF:

0.00142

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 24, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.060

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0054

MetaSVM

Benign

-0.33

PROVEAN

Benign

0.13

REVEL

Benign

0.28

Sift

Benign

0.030

Sift4G

Benign

0.38

Polyphen

0.56

Vest4

0.49

MVP

0.79

ClinPred

0.038

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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