Genetic Variant AGER:c.356-57C>T (chr6-32183445-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001136.5(AGER):c.356-57C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,606,784 control chromosomes in the GnomAD database, including 43,015 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 0.20 ( 3849 hom., cov: 33)

Exomes 𝑓: 0.22 ( 39166 hom. )

Consequence

AGER
NM_001136.5 intron

Scores

Splicing: ADA: 0.00002159

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.942

Publications

68 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AGER	NM_001136.5	MANE Select	c.356-57C>T	intron	N/A	NP_001127.1	Q15109-1
AGER	NM_001206929.2		c.356-57C>T	intron	N/A	NP_001193858.1	Q15109-6
AGER	NM_001206932.2		c.314-57C>T	intron	N/A	NP_001193861.1	Q15109-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AGER	ENST00000375076.9	TSL:1 MANE Select	c.356-57C>T	intron	N/A	ENSP00000364217.4	Q15109-1
AGER	ENST00000375069.7	TSL:1	c.356-57C>T	intron	N/A	ENSP00000364210.4	Q15109-6
AGER	ENST00000438221.6	TSL:1	c.356-57C>T	intron	N/A	ENSP00000387887.2	Q15109-4

Frequencies

GnomAD3 genomes

AF:

0.197

AC:

29938

AN:

152124

Hom.:

3840

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0413

Gnomad AMI

AF:

0.298

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.350

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.314

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.223

GnomAD2 exomes

AF:

0.242

AC:

59351

AN:

245564

AF XY:

0.244

show subpopulations

Gnomad AFR exome

AF:

0.0360

Gnomad AMR exome

AF:

0.297

Gnomad ASJ exome

AF:

0.363

Gnomad EAS exome

AF:

0.132

Gnomad FIN exome

AF:

0.314

Gnomad NFE exome

AF:

0.263

Gnomad OTH exome

AF:

0.257

GnomAD4 exome

AF:

0.221

AC:

321864

AN:

1454542

Hom.:

39166

Cov.:

AF XY:

0.223

AC XY:

161689

AN XY:

724018

show subpopulations

African (AFR)

AF:

0.0350

AC:

1166

AN:

33324

American (AMR)

AF:

0.292

AC:

13053

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.362

AC:

9441

AN:

26104

East Asian (EAS)

AF:

0.183

AC:

7277

AN:

39660

South Asian (SAS)

AF:

0.177

AC:

15241

AN:

86128

European-Finnish (FIN)

AF:

0.306

AC:

16020

AN:

52298

Middle Eastern (MID)

AF:

0.304

AC:

1751

AN:

5762

European-Non Finnish (NFE)

AF:

0.222

AC:

245308

AN:

1106406

Other (OTH)

AF:

0.210

AC:

12607

AN:

60166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

15528

31056

46585

62113

77641

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7850

15700

23550

31400

39250

<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:

0.197

AC:

29967

AN:

152242

Hom.:

3849

Cov.:

AF XY:

0.201

AC XY:

14963

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0412

AC:

1711

AN:

41574

American (AMR)

AF:

0.293

AC:

4476

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

1216

AN:

3470

East Asian (EAS)

AF:

0.139

AC:

721

AN:

5182

South Asian (SAS)

AF:

0.161

AC:

777

AN:

4824

European-Finnish (FIN)

AF:

0.314

AC:

3329

AN:

10586

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.248

AC:

16880

AN:

67986

Other (OTH)

AF:

0.228

AC:

483

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1192

2384

3575

4767

5959

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<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:

0.239

Hom.:

20179

Bravo

AF:

0.189

Asia WGS

AF:

0.179

AC:

623

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.8

(source)

DANN

Benign

0.30

PhyloP100

0.94

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000022

dbscSNV1_RF

Benign

0.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over