Variant 6-32182286-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001136.5(AGER):c.925G>A(p.Gly309Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,612,720 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 1 hom. )

Consequence

AGER
NM_001136.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.739

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01218912).

BP6

Variant 6-32182286-C-T is Benign according to our data. Variant chr6-32182286-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 782997.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGER	NM_001136.5 linkuse as main transcript	c.925G>A	p.Gly309Arg	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.925G>A	p.Gly309Arg	missense_variant	8/11	1	NM_001136.5	P1	Q15109-1

Frequencies

GnomAD3 genomes

AF:

0.00130

AC:

197

AN:

151948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000946

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00219

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00100

AC:

247

AN:

246360

Hom.:

AF XY:

0.00112

AC XY:

150

AN XY:

134308

show subpopulations

Gnomad AFR exome

AF:

0.000464

Gnomad AMR exome

AF:

0.000783

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00186

Gnomad OTH exome

AF:

0.000988

GnomAD4 exome

AF:

0.00148

AC:

2163

AN:

1460650

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

1092

AN XY:

726640

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.000783

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000575

Gnomad4 NFE exome

AF:

0.00181

Gnomad4 OTH exome

AF:

0.00156

GnomAD4 genome

AF:

0.00130

AC:

197

AN:

152070

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.000434

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000946

Gnomad4 NFE

AF:

0.00219

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00215

Hom.:

Bravo

AF:

0.00151

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00133

AC:

ESP6500EA

AF:

0.00185

AC:

ExAC

AF:

0.00108

AC:

127

EpiCase

AF:

0.00294

EpiControl

AF:

0.00367

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.59

Cadd

Benign

Dann

Benign

0.94

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.71

T;T;T;.;T;.

M_CAP

Benign

0.011

MetaRNN

Benign

0.012

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;.;.;.;M;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.2

N;N;.;.;N;.

REVEL

Benign

0.14

Sift

Benign

0.11

T;D;.;.;D;.

Sift4G

Uncertain

0.024

D;D;D;D;D;D

Polyphen

0.058

B;.;.;P;B;.

Vest4

0.38

MutPred

0.57

Gain of solvent accessibility (P = 0.0674);.;.;.;Gain of solvent accessibility (P = 0.0674);.;

MVP

0.52

MPC

0.29

ClinPred

0.018

GERP RS

1.9

Varity_R

0.12

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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