rs3134940

Variant names:

• chr6-32182039-T-C
• rs3134940
• NM_001136.5:c.964+208A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong 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
• Publications: 76 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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 rank	MANE	Protein	UniProt
AGER	NM_001136.5	c.964+208A>G		intron_variant	Intron 8 of 10	ENST00000375076.9	NP_001127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGER	ENST00000375076.9	c.964+208A>G		intron_variant	Intron 8 of 10	1	NM_001136.5	ENSP00000364217.4

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

GnomAD2 exomes AF: 0.130 AC: 16773 AN: 129178 AF XY: 0.132

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 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

African (AFR) AF: 0.116 AC: 2031 AN: 17548

American (AMR) AF: 0.0780 AC: 2694 AN: 34526

Ashkenazi Jewish (ASJ) AF: 0.0919 AC: 1878 AN: 20434

East Asian (EAS) AF: 0.0964 AC: 3131 AN: 32472

South Asian (SAS) AF: 0.126 AC: 8091 AN: 63996

European-Finnish (FIN) AF: 0.139 AC: 4664 AN: 33508

Middle Eastern (MID) AF: 0.0633 AC: 254 AN: 4012

European-Non Finnish (NFE) AF: 0.181 AC: 74525 AN: 412040

Other (OTH) AF: 0.155 AC: 5239 AN: 33808

GnomAD4 genome AF: 0.142 AC: 21574 AN: 152228 Hom.: 1690 Cov.: 33 AF XY: 0.137 AC XY: 10217 AN XY: 74416

African (AFR) AF: 0.110 AC: 4566 AN: 41546

American (AMR) AF: 0.0805 AC: 1231 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0873 AC: 303 AN: 3472

East Asian (EAS) AF: 0.104 AC: 540 AN: 5178

South Asian (SAS) AF: 0.154 AC: 744 AN: 4824

European-Finnish (FIN) AF: 0.138 AC: 1460 AN: 10602

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12223 AN: 68002

Other (OTH) AF: 0.128 AC: 270 AN: 2112

Alfa AF: 0.171 Hom.: 3838

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

Aug 10, 2023

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance: Likely risk allele

Review Status: no assertion criteria provided

Collection Method: research

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
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3134940; hg19: chr6-32149816;