rs2269422

Variant names:

• chr6-32183517-T-C
• rs2269422
• NM_001136.5:c.355+38A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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 -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.

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.355+38A>G		intron	N/A	NP_001127.1	Q15109-1
	AGER	NM_001206929.2		c.355+38A>G		intron	N/A	NP_001193858.1	Q15109-6
	AGER	NM_001206932.2		c.313+38A>G		intron	N/A	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.355+38A>G		intron	N/A	ENSP00000364217.4	Q15109-1
	AGER	ENST00000375069.7	TSL:1	c.355+38A>G		intron	N/A	ENSP00000364210.4	Q15109-6
	AGER	ENST00000438221.6	TSL:1	c.355+38A>G		intron	N/A	ENSP00000387887.2	Q15109-4

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

GnomAD2 exomes AF: 0.0168 AC: 4131 AN: 246364 AF XY: 0.0179

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 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

African (AFR) AF: 0.00108 AC: 36 AN: 33478

American (AMR) AF: 0.00872 AC: 390 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00111 AC: 29 AN: 26136

East Asian (EAS) AF: 0.0789 AC: 3134 AN: 39700

South Asian (SAS) AF: 0.0492 AC: 4246 AN: 86252

European-Finnish (FIN) AF: 0.000459 AC: 24 AN: 52308

Middle Eastern (MID) AF: 0.0165 AC: 95 AN: 5768

European-Non Finnish (NFE) AF: 0.00102 AC: 1137 AN: 1111762

Other (OTH) AF: 0.0124 AC: 751 AN: 60380

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

African (AFR) AF: 0.00149 AC: 62 AN: 41520

American (AMR) AF: 0.00602 AC: 92 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.109 AC: 564 AN: 5172

South Asian (SAS) AF: 0.0677 AC: 326 AN: 4814

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00140 AC: 95 AN: 67998

Other (OTH) AF: 0.00664 AC: 14 AN: 2110

Alfa AF: 0.00204 Hom.: 6

Bravo AF: 0.00643

Asia WGS AF: 0.0670 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.15
DANN	Benign	0.51
PhyloP100		-1.9
Mutation Taster		=100/0	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: rs2269422; hg19: chr6-32151294; COSMIC: COSV107496646; COSMIC: COSV107496646;