Variant rs3134940 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP5BP4BA1

The NM_001136.5(AGER):c.964+208A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 804,572 control chromosomes in the GnomAD database, including 10,778 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely risk allele (no stars).

Frequency

Genomes: 𝑓 0.14 ( 1690 hom., cov: 33)

Exomes 𝑓: 0.16 ( 9088 hom. )

Consequence

AGER
NM_001136.5 intron

Scores

Clinical Significance

Likely risk allele no assertion criteria provided P:1

Conservation

PhyloP100: -0.753

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 Benign. Variant got -8 ACMG points.

PP5

Variant 6-32182039-T-C is Pathogenic according to our data. Variant chr6-32182039-T-C is described in ClinVar as [Likely_risk_allele]. Clinvar id is 2582839.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_pathogenic, oryginal submission is: [Likely_risk_allele].

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91). . Strength limited to SUPPORTING due to the PP5.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGER	NM_001136.5 linkuse as main transcript	c.964+208A>G		intron_variant		ENST00000375076.9	NP_001127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGER	ENST00000375076.9 linkuse as main transcript	c.964+208A>G		intron_variant		1	NM_001136.5	ENSP00000364217	P1	Q15109-1

Frequencies

GnomAD3 genomes

AF:

0.142

AC:

21584

AN:

152108

Hom.:

1695

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.0809

Gnomad ASJ

AF:

0.0873

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.128

GnomAD3 exomes

AF:

0.130

AC:

16773

AN:

129178

Hom.:

1300

AF XY:

0.132

AC XY:

9340

AN XY:

70526

show subpopulations

Gnomad AFR exome

AF:

0.117

Gnomad AMR exome

AF:

0.0733

Gnomad ASJ exome

AF:

0.0887

Gnomad EAS exome

AF:

0.0871

Gnomad SAS exome

AF:

0.126

Gnomad FIN exome

AF:

0.141

Gnomad NFE exome

AF:

0.177

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.157

AC:

102507

AN:

652344

Hom.:

9088

Cov.:

AF XY:

0.156

AC XY:

54006

AN XY:

346268

show subpopulations

Gnomad4 AFR exome

AF:

0.116

Gnomad4 AMR exome

AF:

0.0780

Gnomad4 ASJ exome

AF:

0.0919

Gnomad4 EAS exome

AF:

0.0964

Gnomad4 SAS exome

AF:

0.126

Gnomad4 FIN exome

AF:

0.139

Gnomad4 NFE exome

AF:

0.181

Gnomad4 OTH exome

AF:

0.155

GnomAD4 genome

AF:

0.142

AC:

21574

AN:

152228

Hom.:

1690

Cov.:

AF XY:

0.137

AC XY:

10217

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.0805

Gnomad4 ASJ

AF:

0.0873

Gnomad4 EAS

AF:

0.104

Gnomad4 SAS

AF:

0.154

Gnomad4 FIN

AF:

0.138

Gnomad4 NFE

AF:

0.180

Gnomad4 OTH

AF:

0.128

Alfa

AF:

0.162

Hom.:

1832

Bravo

AF:

0.138

Asia WGS

AF:

0.114

AC:

396

AN:

3478

ClinVar

Significance: Likely risk allele

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

COPD, severe early onset

Pathogenic:1

Likely risk allele, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Aug 10, 2023

Differences in plasma levels of sRAGE according to genotypes -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.1

DANN

Benign

0.43

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

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