rs1035798

chr6-32183445-G-A

Variant summary

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

The NM_001136.5(AGER):c.356-57C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,606,784 control chromosomes in the GnomAD database, including 43,015 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 0.20 (3849 hom., cov: 33)
  • Exomes 𝑓: 0.22 (39166 hom.)
• Consequence: AGER NM_001136.5 intron
• Scores: Splicing: ADA: 0.00002159
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.942

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 (AMR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGER	NM_001136.5	c.356-57C>T		intron_variant		ENST00000375076.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGER	ENST00000375076.9	c.356-57C>T		intron_variant		1	NM_001136.5	P1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29938 AN: 152124 Hom.: 3840 Cov.: 33

Gnomad AFR AF: 0.0413

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.223

GnomAD3 exomes AF: 0.242 AC: 59351 AN: 245564 Hom.: 8249 AF XY: 0.244 AC XY: 32679 AN XY: 134084

Gnomad AFR exome AF: 0.0360

Gnomad AMR exome AF: 0.297

Gnomad ASJ exome AF: 0.363

Gnomad EAS exome AF: 0.132

Gnomad SAS exome AF: 0.173

Gnomad FIN exome AF: 0.314

Gnomad NFE exome AF: 0.263

Gnomad OTH exome AF: 0.257

GnomAD4 exome AF: 0.221 AC: 321864 AN: 1454542 Hom.: 39166 Cov.: 33 AF XY: 0.223 AC XY: 161689 AN XY: 724018

Gnomad4 AFR exome AF: 0.0350

Gnomad4 AMR exome AF: 0.292

Gnomad4 ASJ exome AF: 0.362

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.177

Gnomad4 FIN exome AF: 0.306

Gnomad4 NFE exome AF: 0.222

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.197 AC: 29967 AN: 152242 Hom.: 3849 Cov.: 33 AF XY: 0.201 AC XY: 14963 AN XY: 74416

Gnomad4 AFR AF: 0.0412

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.228

Alfa AF: 0.249 Hom.: 10485

Bravo AF: 0.189

Asia WGS AF: 0.179 AC: 623 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	6.8
Dann	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000022
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.050		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: rs1035798; hg19: chr6-32151222; COSMIC: COSV66719998; COSMIC: COSV66719998;