rs2269422

Positions:

• chr6-32183517-T-C

Variant summary

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

The NM_001136.5(AGER):​c.355+38A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00683 in 1,612,698 control chromosomes in the GnomAD database, including 434 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 0.0077 (69 hom., cov: 33)
  • Exomes 𝑓: 0.0067 (365 hom.)
• Consequence: AGER NM_001136.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGER	NM_001136.5	c.355+38A>G		intron_variant		ENST00000375076.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGER	ENST00000375076.9	c.355+38A>G		intron_variant		1	NM_001136.5	P1

Frequencies

GnomAD3 genomes AF: 0.00769 AC: 1170 AN: 152072 Hom.: 71 Cov.: 33

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00602

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.0677

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00140

Gnomad OTH AF: 0.00575

GnomAD3 exomes AF: 0.0168 AC: 4131 AN: 246364 Hom.: 201 AF XY: 0.0179 AC XY: 2406 AN XY: 134276

Gnomad AFR exome AF: 0.00179

Gnomad AMR exome AF: 0.00833

Gnomad ASJ exome AF: 0.000702

Gnomad EAS exome AF: 0.117

Gnomad SAS exome AF: 0.0484

Gnomad FIN exome AF: 0.000324

Gnomad NFE exome AF: 0.00129

Gnomad OTH exome AF: 0.00857

GnomAD4 exome AF: 0.00674 AC: 9842 AN: 1460508 Hom.: 365 Cov.: 34 AF XY: 0.00802 AC XY: 5830 AN XY: 726580

Gnomad4 AFR exome AF: 0.00108

Gnomad4 AMR exome AF: 0.00872

Gnomad4 ASJ exome AF: 0.00111

Gnomad4 EAS exome AF: 0.0789

Gnomad4 SAS exome AF: 0.0492

Gnomad4 FIN exome AF: 0.000459

Gnomad4 NFE exome AF: 0.00102

Gnomad4 OTH exome AF: 0.0124

GnomAD4 genome AF: 0.00765 AC: 1165 AN: 152190 Hom.: 69 Cov.: 33 AF XY: 0.00934 AC XY: 695 AN XY: 74412

Gnomad4 AFR AF: 0.00149

Gnomad4 AMR AF: 0.00602

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.0677

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00140

Gnomad4 OTH AF: 0.00664

Alfa AF: 0.00188 Hom.: 3

Bravo AF: 0.00643

Asia WGS AF: 0.0670 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.15
DANN	Benign	0.51

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: rs2269422; hg19: chr6-32151294;