Genetic Variant NM_001136.5:c.964+141G>A (chr6-32182106-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001136.5(AGER):c.964+141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 1,198,878 control chromosomes in the GnomAD database, including 2,402 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 0.066 ( 404 hom., cov: 32)

Exomes 𝑓: 0.055 ( 1998 hom. )

Consequence

AGER
NM_001136.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.125

Publications

18 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGER	NM_001136.5 link	c.964+141G>A		intron_variant	Intron 8 of 10	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.964+141G>A		intron_variant	Intron 8 of 10	1	NM_001136.5	ENSP00000364217.4		Q15109-1

Frequencies

GnomAD3 genomes

AF:

0.0659

AC:

10012

AN:

151972

Hom.:

406

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.0653

Gnomad ASJ

AF:

0.0695

Gnomad EAS

AF:

0.0656

Gnomad SAS

AF:

0.0750

Gnomad FIN

AF:

0.00302

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0469

Gnomad OTH

AF:

0.0722

GnomAD2 exomes

AF:

0.0519

AC:

8514

AN:

164180

AF XY:

0.0524

show subpopulations

Gnomad AFR exome

AF:

0.104

Gnomad AMR exome

AF:

0.0499

Gnomad ASJ exome

AF:

0.0712

Gnomad EAS exome

AF:

0.0452

Gnomad FIN exome

AF:

0.00415

Gnomad NFE exome

AF:

0.0443

Gnomad OTH exome

AF:

0.0653

GnomAD4 exome

AF:

0.0554

AC:

57981

AN:

1046788

Hom.:

1998

Cov.:

AF XY:

0.0554

AC XY:

29580

AN XY:

534120

show subpopulations

African (AFR)

AF:

0.108

AC:

2682

AN:

24942

American (AMR)

AF:

0.0529

AC:

1990

AN:

37638

Ashkenazi Jewish (ASJ)

AF:

0.0722

AC:

1677

AN:

23222

East Asian (EAS)

AF:

0.0954

AC:

3360

AN:

35208

South Asian (SAS)

AF:

0.0704

AC:

5245

AN:

74494

European-Finnish (FIN)

AF:

0.00510

AC:

195

AN:

38204

Middle Eastern (MID)

AF:

0.0511

AC:

254

AN:

4970

European-Non Finnish (NFE)

AF:

0.0522

AC:

39696

AN:

761034

Other (OTH)

AF:

0.0612

AC:

2882

AN:

47076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

2921

5842

8764

11685

14606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1392

2784

4176

5568

6960

<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:

0.0659

AC:

10020

AN:

152090

Hom.:

404

Cov.:

AF XY:

0.0635

AC XY:

4722

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.113

AC:

4665

AN:

41466

American (AMR)

AF:

0.0653

AC:

997

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0695

AC:

241

AN:

3466

East Asian (EAS)

AF:

0.0656

AC:

339

AN:

5170

South Asian (SAS)

AF:

0.0752

AC:

362

AN:

4812

European-Finnish (FIN)

AF:

0.00302

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0469

AC:

3186

AN:

67974

Other (OTH)

AF:

0.0710

AC:

150

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

452

905

1357

1810

2262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<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:

0.0503

Hom.:

471

Bravo

AF:

0.0726

Asia WGS

AF:

0.0640

AC:

220

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

-0.13

Mutation Taster

=100/0

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

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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