6-32184217-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001136.5(AGER):c.6T>A(p.Ala2=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.884 in 1,612,480 control chromosomes in the GnomAD database, including 631,546 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 0.91 (63848 hom., cov: 33)
  • Exomes 𝑓: 0.88 (567698 hom.)
• Consequence: AGER NM_001136.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.583

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=0.583 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGER	NM_001136.5	c.6T>A	p.Ala2=	synonymous_variant	1/11	ENST00000375076.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGER	ENST00000375076.9	c.6T>A	p.Ala2=	synonymous_variant	1/11	1	NM_001136.5	P1

Frequencies

GnomAD3 genomes AF: 0.914 AC: 139075 AN: 152122 Hom.: 63785 Cov.: 33

Gnomad AFR AF: 0.972

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.936

Gnomad ASJ AF: 0.971

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.973

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.952

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.937

GnomAD3 exomes AF: 0.916 AC: 224740 AN: 245258 Hom.: 103403 AF XY: 0.918 AC XY: 122630 AN XY: 133656

Gnomad AFR exome AF: 0.977

Gnomad AMR exome AF: 0.954

Gnomad ASJ exome AF: 0.975

Gnomad EAS exome AF: 0.998

Gnomad SAS exome AF: 0.975

Gnomad FIN exome AF: 0.873

Gnomad NFE exome AF: 0.870

Gnomad OTH exome AF: 0.908

GnomAD4 exome AF: 0.880 AC: 1285532 AN: 1460240 Hom.: 567698 Cov.: 62 AF XY: 0.884 AC XY: 641858 AN XY: 726398

Gnomad4 AFR exome AF: 0.977

Gnomad4 AMR exome AF: 0.953

Gnomad4 ASJ exome AF: 0.972

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.975

Gnomad4 FIN exome AF: 0.868

Gnomad4 NFE exome AF: 0.860

Gnomad4 OTH exome AF: 0.891

GnomAD4 genome AF: 0.914 AC: 139196 AN: 152240 Hom.: 63848 Cov.: 33 AF XY: 0.916 AC XY: 68194 AN XY: 74434

Gnomad4 AFR AF: 0.972

Gnomad4 AMR AF: 0.936

Gnomad4 ASJ AF: 0.971

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.973

Gnomad4 FIN AF: 0.884

Gnomad4 NFE AF: 0.865

Gnomad4 OTH AF: 0.938

Alfa AF: 0.884 Hom.: 44987

Bravo AF: 0.921

Asia WGS AF: 0.982 AC: 3417 AN: 3478

EpiCase AF: 0.883

EpiControl AF: 0.890

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	5.5
Dann	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1800684; hg19: chr6-32151994;