rs2853807

Variant names:

• chr6-32181795-G-A
• rs2853807
• NM_001136.5:c.965-163C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136.5(AGER):​c.965-163C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 152,004 control chromosomes in the GnomAD database, including 36 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 0.014 (36 hom., cov: 32)
• Consequence: AGER NM_001136.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.068 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGER	NM_001136.5	c.965-163C>T		intron_variant	Intron 8 of 10	ENST00000375076.9	NP_001127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGER	ENST00000375076.9	c.965-163C>T		intron_variant	Intron 8 of 10	1	NM_001136.5	ENSP00000364217.4

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2197 AN: 151884 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.0140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.0547

Gnomad EAS AF: 0.0660

Gnomad SAS AF: 0.0739

Gnomad FIN AF: 0.000476

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.00685

Gnomad OTH AF: 0.0197

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0145 AC: 2199 AN: 152004 Hom.: 36 Cov.: 32 AF XY: 0.0153 AC XY: 1139 AN XY: 74264

African (AFR) AF: 0.0140 AC: 582 AN: 41458

American (AMR) AF: 0.0137 AC: 210 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0547 AC: 190 AN: 3472

East Asian (EAS) AF: 0.0659 AC: 340 AN: 5158

South Asian (SAS) AF: 0.0743 AC: 358 AN: 4816

European-Finnish (FIN) AF: 0.000476 AC: 5 AN: 10512

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00685 AC: 466 AN: 67996

Other (OTH) AF: 0.0190 AC: 40 AN: 2108

Alfa AF: 0.00885 Hom.: 2

Bravo AF: 0.0134

Asia WGS AF: 0.0580 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.54
PhyloP100		-0.21
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: rs2853807; hg19: chr6-32149572;