Variant 6-32181483-C-T 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.992-6G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 1,613,186 control chromosomes in the GnomAD database, including 632 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.039 ( 267 hom., cov: 32)

Exomes 𝑓: 0.0095 ( 365 hom. )

Consequence

AGER
NM_001136.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00007161

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: -0.0310

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=-0.47).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 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.992-6G>A		splice_region_variant, splice_polypyrimidine_tract_variant, 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.992-6G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001136.5	ENSP00000364217	P1	Q15109-1

Frequencies

GnomAD3 genomes

AF:

0.0392

AC:

5959

AN:

152146

Hom.:

267

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0347

Gnomad ASJ

AF:

0.0181

Gnomad EAS

AF:

0.0366

Gnomad SAS

AF:

0.0267

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00487

Gnomad OTH

AF:

0.0421

GnomAD3 exomes

AF:

0.0189

AC:

4666

AN:

246984

Hom.:

145

AF XY:

0.0180

AC XY:

2419

AN XY:

134522

show subpopulations

Gnomad AFR exome

AF:

0.111

Gnomad AMR exome

AF:

0.0162

Gnomad ASJ exome

AF:

0.0157

Gnomad EAS exome

AF:

0.0384

Gnomad SAS exome

AF:

0.0303

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00477

Gnomad OTH exome

AF:

0.0158

GnomAD4 exome

AF:

0.00953

AC:

13916

AN:

1460922

Hom.:

365

Cov.:

AF XY:

0.00973

AC XY:

7068

AN XY:

726768

show subpopulations

Gnomad4 AFR exome

AF:

0.116

Gnomad4 AMR exome

AF:

0.0189

Gnomad4 ASJ exome

AF:

0.0165

Gnomad4 EAS exome

AF:

0.0287

Gnomad4 SAS exome

AF:

0.0274

Gnomad4 FIN exome

AF:

0.000324

Gnomad4 NFE exome

AF:

0.00365

Gnomad4 OTH exome

AF:

0.0166

GnomAD4 genome

AF:

0.0392

AC:

5969

AN:

152264

Hom.:

267

Cov.:

AF XY:

0.0390

AC XY:

2903

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.0346

Gnomad4 ASJ

AF:

0.0181

Gnomad4 EAS

AF:

0.0367

Gnomad4 SAS

AF:

0.0267

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00487

Gnomad4 OTH

AF:

0.0417

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.0456

Asia WGS

AF:

0.0360

AC:

127

AN:

3478

EpiCase

AF:

0.00725

EpiControl

AF:

0.00688

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

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

2.9

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000072

dbscSNV1_RF

Benign

0.0060

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