6-32182106-C-T

Variant names:

• chr6-32182106-C-T
• rs204996
• NM_001136.5:c.964+141G>A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001136.5(AGER):​c.964+141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 1,198,878 control chromosomes in the GnomAD database, including 2,402 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 0.066 (404 hom., cov: 32)
  • Exomes 𝑓: 0.055 (1998 hom.)
• Consequence: AGER NM_001136.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGER	NM_001136.5	c.964+141G>A		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.964+141G>A		intron_variant	Intron 8 of 10	1	NM_001136.5	ENSP00000364217.4

Frequencies

GnomAD3 genomes AF: 0.0659 AC: 10012 AN: 151972 Hom.: 406 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0653

Gnomad ASJ AF: 0.0695

Gnomad EAS AF: 0.0656

Gnomad SAS AF: 0.0750

Gnomad FIN AF: 0.00302

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0469

Gnomad OTH AF: 0.0722

GnomAD3 exomes AF: 0.0519 AC: 8514 AN: 164180 Hom.: 279 AF XY: 0.0524 AC XY: 4775 AN XY: 91112

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.0499

Gnomad ASJ exome AF: 0.0712

Gnomad EAS exome AF: 0.0452

Gnomad SAS exome AF: 0.0687

Gnomad FIN exome AF: 0.00415

Gnomad NFE exome AF: 0.0443

Gnomad OTH exome AF: 0.0653

GnomAD4 exome AF: 0.0554 AC: 57981 AN: 1046788 Hom.: 1998 Cov.: 14 AF XY: 0.0554 AC XY: 29580 AN XY: 534120

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.0529

Gnomad4 ASJ exome AF: 0.0722

Gnomad4 EAS exome AF: 0.0954

Gnomad4 SAS exome AF: 0.0704

Gnomad4 FIN exome AF: 0.00510

Gnomad4 NFE exome AF: 0.0522

Gnomad4 OTH exome AF: 0.0612

GnomAD4 genome AF: 0.0659 AC: 10020 AN: 152090 Hom.: 404 Cov.: 32 AF XY: 0.0635 AC XY: 4722 AN XY: 74342

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0653

Gnomad4 ASJ AF: 0.0695

Gnomad4 EAS AF: 0.0656

Gnomad4 SAS AF: 0.0752

Gnomad4 FIN AF: 0.00302

Gnomad4 NFE AF: 0.0469

Gnomad4 OTH AF: 0.0710

Alfa AF: 0.0541 Hom.: 68

Bravo AF: 0.0726

Asia WGS AF: 0.0640 AC: 220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Benign	0.89

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: rs204996; hg19: chr6-32149883; COSMIC: COSV61248179; COSMIC: COSV61248179;