6-32182039-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP5 BP4 BA1

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
• Clinical Significance: Likely risk allele no assertion criteria provided P:1
• Conservation: PhyloP100: -0.753

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]

ACMG classification

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	UniProt
AGER	NM_001136.5	c.964+208A>G		intron_variant		ENST00000375076.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGER	ENST00000375076.9	c.964+208A>G		intron_variant		1	NM_001136.5	P1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21584 AN: 152108 Hom.: 1695 Cov.: 33

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

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.: 8 AF XY: 0.156 AC XY: 54006 AN XY: 346268

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.: 33 AF XY: 0.137 AC XY: 10217 AN XY: 74416

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

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

Other links and lift over

dbSNP: rs3134940; hg19: chr6-32149816;