rs3176931

Variant names:

• chr6-32181363-C-T
• rs3176931
• NM_001136.5:c.1106G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001136.5(AGER):​c.1106G>A​(p.Arg369Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 1,612,674 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (21 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (96 hom.)
• Consequence: AGER NM_001136.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.40
• Publications: 12 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002130419).
• BP6: Variant 6-32181363-C-T is Benign according to our data. Variant chr6-32181363-C-T is described in ClinVar as Benign. ClinVar VariationId is 769678.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0034 (518/152364) while in subpopulation SAS AF = 0.0184 (89/4830). AF 95% confidence interval is 0.0153. There are 21 homozygotes in GnomAd4. There are 239 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136.5. 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.1106G>A	p.Arg369Gln	missense	Exon 10 of 11	NP_001127.1
	AGER	NM_001206929.2		c.1154G>A	p.Arg385Gln	missense	Exon 10 of 11	NP_001193858.1
	AGER	NM_001206932.2		c.1064G>A	p.Arg355Gln	missense	Exon 10 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.1106G>A	p.Arg369Gln	missense	Exon 10 of 11	ENSP00000364217.4
	AGER	ENST00000375069.7	TSL:1	c.1154G>A	p.Arg385Gln	missense	Exon 10 of 11	ENSP00000364210.4
	AGER	ENST00000375067.7	TSL:1	c.951G>A	p.Pro317Pro	synonymous	Exon 9 of 10	ENSP00000364208.3

Frequencies

GnomAD3 genomes AF: 0.00332 AC: 505 AN: 152246 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.0182

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00191

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00738 AC: 1841 AN: 249530 AF XY: 0.00723

Gnomad AFR exome AF: 0.000938

Gnomad AMR exome AF: 0.0239

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.00800

Gnomad FIN exome AF: 0.0000930

Gnomad NFE exome AF: 0.00189

Gnomad OTH exome AF: 0.00558

GnomAD4 exome AF: 0.00347 AC: 5064 AN: 1460310 Hom.: 96 Cov.: 31 AF XY: 0.00402 AC XY: 2917 AN XY: 726380

African (AFR) AF: 0.000719 AC: 24 AN: 33362

American (AMR) AF: 0.0236 AC: 1049 AN: 44532

Ashkenazi Jewish (ASJ) AF: 0.0000768 AC: 2 AN: 26052

East Asian (EAS) AF: 0.00615 AC: 244 AN: 39676

South Asian (SAS) AF: 0.0204 AC: 1756 AN: 86228

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53290

Middle Eastern (MID) AF: 0.0167 AC: 96 AN: 5758

European-Non Finnish (NFE) AF: 0.00123 AC: 1368 AN: 1111104

Other (OTH) AF: 0.00852 AC: 514 AN: 60308

GnomAD4 genome AF: 0.00340 AC: 518 AN: 152364 Hom.: 21 Cov.: 32 AF XY: 0.00321 AC XY: 239 AN XY: 74508

African (AFR) AF: 0.00115 AC: 48 AN: 41592

American (AMR) AF: 0.0113 AC: 173 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0110 AC: 57 AN: 5180

South Asian (SAS) AF: 0.0184 AC: 89 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10630

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00191 AC: 130 AN: 68036

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.00332 Hom.: 13

Bravo AF: 0.00357

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.00165 AC: 5

ESP6500EA AF: 0.00277 AC: 15

ExAC AF: 0.00730 AC: 886

Asia WGS AF: 0.0460 AC: 160 AN: 3478

EpiCase AF: 0.00305

EpiControl AF: 0.00255

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.99
DANN	Benign	0.81
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.1	T
PhyloP100		-2.4
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.039
Sift	Benign	0.53	T
Sift4G	Benign	0.70	T
Polyphen		0.0070	B
Vest4		0.096
MVP		0.072
MPC		0.18
ClinPred		0.0030	T
GERP RS		-8.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.017
gMVP		0.18
Mutation Taster		=98/2	polymorphism

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: rs3176931; hg19: chr6-32149140;