6-32182286-C-T

Variant names:

• chr6-32182286-C-T
• rs138186526
• NM_001136.5:c.925G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001136.5(AGER):​c.925G>A​(p.Gly309Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,612,720 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (1 hom.)
• Consequence: AGER NM_001136.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.739
• Publications: 5 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01218912).
• BP6: Variant 6-32182286-C-T is Benign according to our data. Variant chr6-32182286-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 782997.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGER	NM_001136.5	MANE Select	c.925G>A	p.Gly309Arg	missense	Exon 8 of 11	NP_001127.1	Q15109-1
	AGER	NM_001206929.2		c.973G>A	p.Gly325Arg	missense	Exon 8 of 11	NP_001193858.1	Q15109-6
	AGER	NM_001206932.2		c.883G>A	p.Gly295Arg	missense	Exon 8 of 11	NP_001193861.1	Q15109-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGER	ENST00000375076.9	TSL:1 MANE Select	c.925G>A	p.Gly309Arg	missense	Exon 8 of 11	ENSP00000364217.4	Q15109-1
	AGER	ENST00000375069.7	TSL:1	c.973G>A	p.Gly325Arg	missense	Exon 8 of 11	ENSP00000364210.4	Q15109-6
	AGER	ENST00000438221.6	TSL:1	c.973G>A	p.Gly325Arg	missense	Exon 8 of 10	ENSP00000387887.2	Q15109-4

Frequencies

GnomAD3 genomes AF: 0.00130 AC: 197 AN: 151948 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00219

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00100 AC: 247 AN: 246360 AF XY: 0.00112

Gnomad AFR exome AF: 0.000464

Gnomad AMR exome AF: 0.000783

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00186

Gnomad OTH exome AF: 0.000988

GnomAD4 exome AF: 0.00148 AC: 2163 AN: 1460650 Hom.: 1 Cov.: 34 AF XY: 0.00150 AC XY: 1092 AN XY: 726640

African (AFR) AF: 0.000448 AC: 15 AN: 33480

American (AMR) AF: 0.000783 AC: 35 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000575 AC: 3 AN: 52192

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00181 AC: 2012 AN: 1112006

Other (OTH) AF: 0.00156 AC: 94 AN: 60386

GnomAD4 genome AF: 0.00130 AC: 197 AN: 152070 Hom.: 0 Cov.: 32 AF XY: 0.00124 AC XY: 92 AN XY: 74334

African (AFR) AF: 0.000434 AC: 18 AN: 41492

American (AMR) AF: 0.00170 AC: 26 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.0000946 AC: 1 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00219 AC: 149 AN: 67972

Other (OTH) AF: 0.00142 AC: 3 AN: 2108

Alfa AF: 0.00194 Hom.: 0

Bravo AF: 0.00151

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.00133 AC: 4

ESP6500EA AF: 0.00185 AC: 10

ExAC AF: 0.00108 AC: 127

EpiCase AF: 0.00294

EpiControl AF: 0.00367

ClinVar

ClinVar submissions as Germline

Significance: Likely 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	0.083
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.74
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.14
Sift	Benign	0.11	T
Sift4G	Uncertain	0.024	D
Polyphen		0.058	B
Vest4		0.38
MutPred		0.57		Gain of solvent accessibility (P = 0.0674)
MVP		0.52
MPC		0.29
ClinPred		0.018	T
GERP RS		1.9
Varity_R		0.12
gMVP		0.53
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs138186526; hg19: chr6-32150063;