dbSNP rs3176931: AGER:p.Arg369Gln (chr6-32181363-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001136.5(AGER):c.1106G>A(p.Arg369Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 1,612,674 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 21 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 96 hom. )

Consequence

AGER
NM_001136.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.40

Publications

12 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002130419).

BP6

Variant 6-32181363-C-T is Benign according to our data. Variant chr6-32181363-C-T is described in ClinVar as [Benign]. Clinvar id is 769678.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0034 (518/152364) while in subpopulation SAS AF = 0.0184 (89/4830). AF 95% confidence interval is 0.0153. There are 21 homozygotes in GnomAd4. There are 239 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGER	NM_001136.5 link	c.1106G>A	p.Arg369Gln	missense_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.1106G>A	p.Arg369Gln	missense_variant	Exon 10 of 11	1	NM_001136.5	ENSP00000364217.4		Q15109-1

Frequencies

GnomAD3 genomes

AF:

0.00332

AC:

505

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0110

Gnomad SAS

AF:

0.0182

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00191

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.00738

AC:

1841

AN:

249530

AF XY:

0.00723

show subpopulations

Gnomad AFR exome

AF:

0.000938

Gnomad AMR exome

AF:

0.0239

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00800

Gnomad FIN exome

AF:

0.0000930

Gnomad NFE exome

AF:

0.00189

Gnomad OTH exome

AF:

0.00558

GnomAD4 exome

AF:

0.00347

AC:

5064

AN:

1460310

Hom.:

Cov.:

AF XY:

0.00402

AC XY:

2917

AN XY:

726380

show subpopulations

African (AFR)

AF:

0.000719

AC:

AN:

33362

American (AMR)

AF:

0.0236

AC:

1049

AN:

44532

Ashkenazi Jewish (ASJ)

AF:

0.0000768

AC:

AN:

26052

East Asian (EAS)

AF:

0.00615

AC:

244

AN:

39676

South Asian (SAS)

AF:

0.0204

AC:

1756

AN:

86228

European-Finnish (FIN)

AF:

0.000206

AC:

AN:

53290

Middle Eastern (MID)

AF:

0.0167

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00123

AC:

1368

AN:

1111104

Other (OTH)

AF:

0.00852

AC:

514

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

323

646

969

1292

1615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00340

AC:

518

AN:

152364

Hom.:

Cov.:

AF XY:

0.00321

AC XY:

239

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.00115

AC:

AN:

41592

American (AMR)

AF:

0.0113

AC:

173

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0110

AC:

AN:

5180

South Asian (SAS)

AF:

0.0184

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00191

AC:

130

AN:

68036

Other (OTH)

AF:

0.00804

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

122

153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00332

Hom.:

Bravo

AF:

0.00357

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00165

AC:

ESP6500EA

AF:

0.00277

AC:

ExAC

AF:

0.00730

AC:

886

Asia WGS

AF:

0.0460

AC:

160

AN:

3478

EpiCase

AF:

0.00305

EpiControl

AF:

0.00255

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 31, 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

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.99

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.0057

.;T;.;T;T

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.41

T;T;.;T;.

MetaRNN

Benign

0.0021

T;T;T;T;T

MetaSVM

Benign

-1.1

PhyloP100

-2.4

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.47

.;.;N;N;N

REVEL

Benign

0.039

Sift

Benign

0.53

.;.;T;T;D

Sift4G

Benign

0.70

T;T;T;T;T

Polyphen

0.0070, 0.0030

.;.;B;B;.

Vest4

0.096

MVP

0.072

MPC

0.18

ClinPred

0.0030

GERP RS

-8.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.017

gMVP

0.18

Mutation Taster

=98/2

polymorphism

(source)

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

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rs3176931

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over