6-32184217-A-T

Variant names:

• chr6-32184217-A-T
• rs1800684
• NM_001136.5:c.6T>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001136.5(AGER):​c.6T>A​(p.Ala2Ala) 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
• Publications: 86 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 -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.

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.6T>A	p.Ala2Ala	synonymous	Exon 1 of 11	NP_001127.1	Q15109-1
	AGER	NM_001206929.2		c.6T>A	p.Ala2Ala	synonymous	Exon 1 of 11	NP_001193858.1	Q15109-6
	AGER	NM_001206932.2		c.6T>A	p.Ala2Ala	synonymous	Exon 1 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.6T>A	p.Ala2Ala	synonymous	Exon 1 of 11	ENSP00000364217.4	Q15109-1
	AGER	ENST00000375069.7	TSL:1	c.6T>A	p.Ala2Ala	synonymous	Exon 1 of 11	ENSP00000364210.4	Q15109-6
	AGER	ENST00000438221.6	TSL:1	c.6T>A	p.Ala2Ala	synonymous	Exon 1 of 10	ENSP00000387887.2	Q15109-4

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

GnomAD2 exomes AF: 0.916 AC: 224740 AN: 245258 AF XY: 0.918

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 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

African (AFR) AF: 0.977 AC: 32702 AN: 33472

American (AMR) AF: 0.953 AC: 42560 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.972 AC: 25370 AN: 26102

East Asian (EAS) AF: 0.999 AC: 39638 AN: 39696

South Asian (SAS) AF: 0.975 AC: 84015 AN: 86198

European-Finnish (FIN) AF: 0.868 AC: 45425 AN: 52306

Middle Eastern (MID) AF: 0.946 AC: 5452 AN: 5762

European-Non Finnish (NFE) AF: 0.860 AC: 956590 AN: 1111670

Other (OTH) AF: 0.891 AC: 53780 AN: 60356

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

African (AFR) AF: 0.972 AC: 40377 AN: 41540

American (AMR) AF: 0.936 AC: 14325 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.971 AC: 3370 AN: 3472

East Asian (EAS) AF: 0.995 AC: 5150 AN: 5174

South Asian (SAS) AF: 0.973 AC: 4703 AN: 4834

European-Finnish (FIN) AF: 0.884 AC: 9379 AN: 10606

Middle Eastern (MID) AF: 0.949 AC: 277 AN: 292

European-Non Finnish (NFE) AF: 0.865 AC: 58786 AN: 67992

Other (OTH) AF: 0.938 AC: 1983 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.5
DANN	Benign	0.82
PhyloP100		0.58
PromoterAI		-0.045	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

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: rs1800684; hg19: chr6-32151994;