6-32183666-C-T

Variant names:

• chr6-32183666-C-T
• rs2070600
• NM_001136.5:c.244G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3 BA1

The NM_001206929.2(AGER):​c.244G>A​(p.Gly82Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0561 in 1,613,010 control chromosomes in the GnomAD database, including 3,365 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 0.039 (234 hom., cov: 33)
  • Exomes 𝑓: 0.058 (3131 hom.)
• Consequence: AGER NM_001206929.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.46
• Publications: 465 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 -7 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206929.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGER	NM_001136.5	MANE Select	c.244G>A	p.Gly82Ser	missense	Exon 3 of 11	NP_001127.1
	AGER	NM_001206929.2		c.244G>A	p.Gly82Ser	missense	Exon 3 of 11	NP_001193858.1
	AGER	NM_001206932.2		c.202G>A	p.Gly68Ser	missense	Exon 3 of 11	NP_001193861.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGER	ENST00000375076.9	TSL:1 MANE Select	c.244G>A	p.Gly82Ser	missense	Exon 3 of 11	ENSP00000364217.4
	AGER	ENST00000375069.7	TSL:1	c.244G>A	p.Gly82Ser	missense	Exon 3 of 11	ENSP00000364210.4
	AGER	ENST00000438221.6	TSL:1	c.244G>A	p.Gly82Ser	missense	Exon 3 of 10	ENSP00000387887.2

Frequencies

GnomAD3 genomes AF: 0.0388 AC: 5905 AN: 152132 Hom.: 234 Cov.: 33

Gnomad AFR AF: 0.00990

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.00981

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.0614

Gnomad FIN AF: 0.0702

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0456

Gnomad OTH AF: 0.0239

GnomAD2 exomes AF: 0.0532 AC: 13091 AN: 245924 AF XY: 0.0540

Gnomad AFR exome AF: 0.00921

Gnomad AMR exome AF: 0.00676

Gnomad ASJ exome AF: 0.0107

Gnomad EAS exome AF: 0.207

Gnomad FIN exome AF: 0.0686

Gnomad NFE exome AF: 0.0463

Gnomad OTH exome AF: 0.0409

GnomAD4 exome AF: 0.0580 AC: 84662 AN: 1460760 Hom.: 3131 Cov.: 36 AF XY: 0.0575 AC XY: 41809 AN XY: 726696

African (AFR) AF: 0.00765 AC: 256 AN: 33480

American (AMR) AF: 0.00738 AC: 330 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00983 AC: 257 AN: 26136

East Asian (EAS) AF: 0.174 AC: 6889 AN: 39700

South Asian (SAS) AF: 0.0622 AC: 5368 AN: 86258

European-Finnish (FIN) AF: 0.0647 AC: 3382 AN: 52308

Middle Eastern (MID) AF: 0.0134 AC: 77 AN: 5766

European-Non Finnish (NFE) AF: 0.0583 AC: 64846 AN: 1112002

Other (OTH) AF: 0.0539 AC: 3257 AN: 60386

GnomAD4 genome AF: 0.0387 AC: 5895 AN: 152250 Hom.: 234 Cov.: 33 AF XY: 0.0403 AC XY: 3002 AN XY: 74448

African (AFR) AF: 0.00987 AC: 410 AN: 41540

American (AMR) AF: 0.00980 AC: 150 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00980 AC: 34 AN: 3468

East Asian (EAS) AF: 0.206 AC: 1068 AN: 5184

South Asian (SAS) AF: 0.0611 AC: 295 AN: 4830

European-Finnish (FIN) AF: 0.0702 AC: 744 AN: 10604

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0456 AC: 3102 AN: 67998

Other (OTH) AF: 0.0241 AC: 51 AN: 2114

Alfa AF: 0.0435 Hom.: 735

Bravo AF: 0.0339

TwinsUK AF: 0.0655 AC: 243

ALSPAC AF: 0.0804 AC: 310

ESP6500AA AF: 0.0156 AC: 47

ESP6500EA AF: 0.0456 AC: 247

ExAC AF: 0.0530 AC: 6195

Asia WGS AF: 0.104 AC: 361 AN: 3478

EpiCase AF: 0.0405

EpiControl AF: 0.0414

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	COPD, severe early onset (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.5
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.16
Sift	Benign	0.51	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.69
MPC		0.65
ClinPred		0.040	T
GERP RS		5.8
Varity_R		0.20
gMVP		0.43
Mutation Taster		=87/13	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.73		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.73		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2070600; hg19: chr6-32151443; COSMIC: COSV107496643; COSMIC: COSV107496643;