rs143357175

Variant names:

• chr6-32181442-G-A
• rs143357175
• ENST00000375067.7:c.872C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_172197.3(AGER):​c.872C>T​(p.Pro291Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,613,364 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (11 hom.)
• Consequence: AGER NM_172197.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.44
• Publications: 9 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0054189563).
• BP6: Variant 6-32181442-G-A is Benign according to our data. Variant chr6-32181442-G-A is described in ClinVar as Benign. ClinVar VariationId is 735622.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172197.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGER	NM_001136.5	MANE Select	c.1027C>T	p.Leu343Leu	synonymous	Exon 10 of 11	NP_001127.1	Q15109-1
	AGER	NM_172197.3		c.872C>T	p.Pro291Leu	missense	Exon 9 of 10	NP_751947.1	Q15109-2
	AGER	NM_001206929.2		c.1075C>T	p.Leu359Leu	synonymous	Exon 10 of 11	NP_001193858.1	Q15109-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGER	ENST00000375067.7	TSL:1	c.872C>T	p.Pro291Leu	missense	Exon 9 of 10	ENSP00000364208.3	Q15109-2
	AGER	ENST00000375076.9	TSL:1 MANE Select	c.1027C>T	p.Leu343Leu	synonymous	Exon 10 of 11	ENSP00000364217.4	Q15109-1
	AGER	ENST00000375069.7	TSL:1	c.1075C>T	p.Leu359Leu	synonymous	Exon 10 of 11	ENSP00000364210.4	Q15109-6

Frequencies

GnomAD3 genomes AF: 0.00112 AC: 171 AN: 152184 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.00637

Gnomad SAS AF: 0.00683

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000809

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00202 AC: 499 AN: 247318 AF XY: 0.00224

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000348

Gnomad ASJ exome AF: 0.00784

Gnomad EAS exome AF: 0.00503

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00107

Gnomad OTH exome AF: 0.00297

GnomAD4 exome AF: 0.00121 AC: 1768 AN: 1461062 Hom.: 11 Cov.: 31 AF XY: 0.00141 AC XY: 1027 AN XY: 726816

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.000515 AC: 23 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00866 AC: 226 AN: 26104

East Asian (EAS) AF: 0.00282 AC: 112 AN: 39700

South Asian (SAS) AF: 0.00645 AC: 556 AN: 86250

European-Finnish (FIN) AF: 0.0000758 AC: 4 AN: 52790

Middle Eastern (MID) AF: 0.00885 AC: 51 AN: 5764

European-Non Finnish (NFE) AF: 0.000594 AC: 661 AN: 1111932

Other (OTH) AF: 0.00222 AC: 134 AN: 60374

GnomAD4 genome AF: 0.00112 AC: 171 AN: 152302 Hom.: 3 Cov.: 32 AF XY: 0.00113 AC XY: 84 AN XY: 74472

African (AFR) AF: 0.0000241 AC: 1 AN: 41574

American (AMR) AF: 0.000523 AC: 8 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3470

East Asian (EAS) AF: 0.00638 AC: 33 AN: 5170

South Asian (SAS) AF: 0.00683 AC: 33 AN: 4830

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.000809 AC: 55 AN: 68016

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.00145 Hom.: 0

Bravo AF: 0.00104

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000738 AC: 4

ExAC AF: 0.00219 AC: 264

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.00174

EpiControl AF: 0.00142

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	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Uncertain	0.060
CADD	Benign	11
DANN	Uncertain	1.0
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0054	T
MetaSVM	Benign	-0.33	T
PhyloP100		2.4
PROVEAN	Benign	0.13	N
REVEL	Benign	0.28
Sift	Benign	0.030	D
Sift4G	Benign	0.38	T
Polyphen		0.56	P
Vest4		0.49
MVP		0.79
ClinPred		0.038	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=92/8	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: rs143357175; hg19: chr6-32149219;