rs184003

Variant names:

• chr6-32182519-C-A
• rs184003
• NM_001136.5:c.822+49G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.113
• Publications: 88 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=-0.81).
• 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 rank	MANE	Protein	UniProt
AGER	NM_001136.5	c.822+49G>T		intron_variant	Intron 7 of 10	ENST00000375076.9	NP_001127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGER	ENST00000375076.9	c.822+49G>T		intron_variant	Intron 7 of 10	1	NM_001136.5	ENSP00000364217.4

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18893 AN: 152074 Hom.: 1574 Cov.: 32

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

GnomAD2 exomes AF: 0.124 AC: 29835 AN: 241434 AF XY: 0.133

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 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.: 34 AF XY: 0.0987 AC XY: 70967 AN XY: 719306

African (AFR) AF: 0.203 AC: 6750 AN: 33196

American (AMR) AF: 0.0883 AC: 3890 AN: 44040

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 4886 AN: 25640

East Asian (EAS) AF: 0.129 AC: 5109 AN: 39456

South Asian (SAS) AF: 0.296 AC: 25272 AN: 85514

European-Finnish (FIN) AF: 0.0506 AC: 2640 AN: 52126

Middle Eastern (MID) AF: 0.263 AC: 1498 AN: 5706

European-Non Finnish (NFE) AF: 0.0686 AC: 75779 AN: 1104342

Other (OTH) AF: 0.114 AC: 6808 AN: 59720

GnomAD4 genome AF: 0.124 AC: 18930 AN: 152192 Hom.: 1579 Cov.: 32 AF XY: 0.127 AC XY: 9449 AN XY: 74412

African (AFR) AF: 0.203 AC: 8417 AN: 41496

American (AMR) AF: 0.118 AC: 1807 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 717 AN: 3470

East Asian (EAS) AF: 0.153 AC: 791 AN: 5172

South Asian (SAS) AF: 0.257 AC: 1237 AN: 4820

European-Finnish (FIN) AF: 0.0455 AC: 483 AN: 10614

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.0732 AC: 4976 AN: 67998

Other (OTH) AF: 0.165 AC: 348 AN: 2110

Alfa AF: 0.0939 Hom.: 1760

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

Submissions by phenotype

COPD, severe early onset Uncertain:1

Aug 10, 2023

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.2
DANN	Benign	0.75
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs184003; hg19: chr6-32150296; COSMIC: COSV61248725; COSMIC: COSV61248725;