rs3131300

Positions:

• chr6-32184157-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136.5(AGER):​c.52+14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,609,916 control chromosomes in the GnomAD database, including 25,894 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1733 hom., cov: 32)
  • Exomes 𝑓: 0.18 (24161 hom.)
• Consequence: AGER NM_001136.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.826

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGER	NM_001136.5	c.52+14T>C		intron_variant		ENST00000375076.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGER	ENST00000375076.9	c.52+14T>C		intron_variant		1	NM_001136.5	P1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21837 AN: 151970 Hom.: 1738 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.0817

Gnomad ASJ AF: 0.0875

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.128

GnomAD3 exomes AF: 0.135 AC: 32805 AN: 242884 Hom.: 2519 AF XY: 0.137 AC XY: 18160 AN XY: 132340

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.0734

Gnomad ASJ exome AF: 0.0906

Gnomad EAS exome AF: 0.0907

Gnomad SAS exome AF: 0.130

Gnomad FIN exome AF: 0.132

Gnomad NFE exome AF: 0.170

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.175 AC: 255563 AN: 1457828 Hom.: 24161 Cov.: 56 AF XY: 0.173 AC XY: 125573 AN XY: 725120

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.0773

Gnomad4 ASJ exome AF: 0.0934

Gnomad4 EAS exome AF: 0.0972

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.170

GnomAD4 genome AF: 0.144 AC: 21827 AN: 152088 Hom.: 1733 Cov.: 32 AF XY: 0.139 AC XY: 10339 AN XY: 74344

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0813

Gnomad4 ASJ AF: 0.0875

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.127

Alfa AF: 0.163 Hom.: 977

Bravo AF: 0.140

Asia WGS AF: 0.114 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.1
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs3131300; hg19: chr6-32151934;