Genetic Variant AGER:p.Ala2Ala (chr6-32184217-A-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001136.5(AGER):c.6T>A(p.Ala2Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.884 in 1,612,480 control chromosomes in the GnomAD database, including 631,546 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.91 ( 63848 hom., cov: 33)

Exomes 𝑓: 0.88 ( 567698 hom. )

Consequence

AGER
NM_001136.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.583

Publications

85 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP7

Synonymous conserved (PhyloP=0.583 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGER	NM_001136.5 link	c.6T>A	p.Ala2Ala	synonymous_variant	Exon 1 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.6T>A	p.Ala2Ala	synonymous_variant	Exon 1 of 11	1	NM_001136.5	ENSP00000364217.4		Q15109-1

Frequencies

GnomAD3 genomes

AF:

0.914

AC:

139075

AN:

152122

Hom.:

63785

Cov.:

show subpopulations

Gnomad AFR

AF:

0.972

Gnomad AMI

AF:

0.928

Gnomad AMR

AF:

0.936

Gnomad ASJ

AF:

0.971

Gnomad EAS

AF:

0.995

Gnomad SAS

AF:

0.973

Gnomad FIN

AF:

0.884

Gnomad MID

AF:

0.952

Gnomad NFE

AF:

0.865

Gnomad OTH

AF:

0.937

GnomAD2 exomes

AF:

0.916

AC:

224740

AN:

245258

AF XY:

0.918

show subpopulations

Gnomad AFR exome

AF:

0.977

Gnomad AMR exome

AF:

0.954

Gnomad ASJ exome

AF:

0.975

Gnomad EAS exome

AF:

0.998

Gnomad FIN exome

AF:

0.873

Gnomad NFE exome

AF:

0.870

Gnomad OTH exome

AF:

0.908

GnomAD4 exome

AF:

0.880

AC:

1285532

AN:

1460240

Hom.:

567698

Cov.:

AF XY:

0.884

AC XY:

641858

AN XY:

726398

show subpopulations

African (AFR)

AF:

0.977

AC:

32702

AN:

33472

American (AMR)

AF:

0.953

AC:

42560

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.972

AC:

25370

AN:

26102

East Asian (EAS)

AF:

0.999

AC:

39638

AN:

39696

South Asian (SAS)

AF:

0.975

AC:

84015

AN:

86198

European-Finnish (FIN)

AF:

0.868

AC:

45425

AN:

52306

Middle Eastern (MID)

AF:

0.946

AC:

5452

AN:

5762

European-Non Finnish (NFE)

AF:

0.860

AC:

956590

AN:

1111670

Other (OTH)

AF:

0.891

AC:

53780

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

8365

16731

25096

33462

41827

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21242

42484

63726

84968

106210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.914

AC:

139196

AN:

152240

Hom.:

63848

Cov.:

AF XY:

0.916

AC XY:

68194

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.972

AC:

40377

AN:

41540

American (AMR)

AF:

0.936

AC:

14325

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.971

AC:

3370

AN:

3472

East Asian (EAS)

AF:

0.995

AC:

5150

AN:

5174

South Asian (SAS)

AF:

0.973

AC:

4703

AN:

4834

European-Finnish (FIN)

AF:

0.884

AC:

9379

AN:

10606

Middle Eastern (MID)

AF:

0.949

AC:

277

AN:

292

European-Non Finnish (NFE)

AF:

0.865

AC:

58786

AN:

67992

Other (OTH)

AF:

0.938

AC:

1983

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

602

1205

1807

2410

3012

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

906

1812

2718

3624

4530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.884

Hom.:

44987

Bravo

AF:

0.921

Asia WGS

AF:

0.982

AC:

3417

AN:

3478

EpiCase

AF:

0.883

EpiControl

AF:

0.890

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

5.5

(source)

DANN

Benign

0.82

PhyloP100

0.58

PromoterAI

-0.045

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over