Variant rs184003 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001136.5(AGER):c.822+49G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0946 in 1,601,932 control chromosomes in the GnomAD database, including 10,864 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.12 ( 1579 hom., cov: 32)

Exomes 𝑓: 0.091 ( 9285 hom. )

Consequence

AGER
NM_001136.5 intron

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.113

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.245 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.822+49G>T		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.822+49G>T		intron_variant		1	NM_001136.5	ENSP00000364217	P1	Q15109-1

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18893

AN:

152074

Hom.:

1574

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.0888

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.207

Gnomad EAS

AF:

0.153

Gnomad SAS

AF:

0.257

Gnomad FIN

AF:

0.0455

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.0732

Gnomad OTH

AF:

0.167

GnomAD3 exomes

AF:

0.124

AC:

29835

AN:

241434

Hom.:

2780

AF XY:

0.133

AC XY:

17494

AN XY:

131616

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.0845

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.174

Gnomad SAS exome

AF:

0.297

Gnomad FIN exome

AF:

0.0486

Gnomad NFE exome

AF:

0.0780

Gnomad OTH exome

AF:

0.115

GnomAD4 exome

AF:

0.0915

AC:

132632

AN:

1449740

Hom.:

9285

Cov.:

AF XY:

0.0987

AC XY:

70967

AN XY:

719306

show subpopulations

Gnomad4 AFR exome

AF:

0.203

Gnomad4 AMR exome

AF:

0.0883

Gnomad4 ASJ exome

AF:

0.191

Gnomad4 EAS exome

AF:

0.129

Gnomad4 SAS exome

AF:

0.296

Gnomad4 FIN exome

AF:

0.0506

Gnomad4 NFE exome

AF:

0.0686

Gnomad4 OTH exome

AF:

0.114

GnomAD4 genome

AF:

0.124

AC:

18930

AN:

152192

Hom.:

1579

Cov.:

AF XY:

0.127

AC XY:

9449

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.203

Gnomad4 AMR

AF:

0.118

Gnomad4 ASJ

AF:

0.207

Gnomad4 EAS

AF:

0.153

Gnomad4 SAS

AF:

0.257

Gnomad4 FIN

AF:

0.0455

Gnomad4 NFE

AF:

0.0732

Gnomad4 OTH

AF:

0.165

Alfa

AF:

0.0987

Hom.:

490

Bravo

AF:

0.131

Asia WGS

AF:

0.239

AC:

835

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

COPD, severe early onset

Uncertain:1

Uncertain significance, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Aug 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.2

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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