6-32182106-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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 -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.

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.964+141G>A		intron	N/A	NP_001127.1	Q15109-1
	AGER	NM_001206929.2		c.1012+141G>A		intron	N/A	NP_001193858.1	Q15109-6
	AGER	NM_001206932.2		c.922+141G>A		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.964+141G>A		intron	N/A	ENSP00000364217.4	Q15109-1
	AGER	ENST00000375069.7	TSL:1	c.1012+141G>A		intron	N/A	ENSP00000364210.4	Q15109-6
	AGER	ENST00000438221.6	TSL:1	c.1012+141G>A		intron	N/A	ENSP00000387887.2	Q15109-4

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

GnomAD2 exomes AF: 0.0519 AC: 8514 AN: 164180 AF XY: 0.0524

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 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

African (AFR) AF: 0.108 AC: 2682 AN: 24942

American (AMR) AF: 0.0529 AC: 1990 AN: 37638

Ashkenazi Jewish (ASJ) AF: 0.0722 AC: 1677 AN: 23222

East Asian (EAS) AF: 0.0954 AC: 3360 AN: 35208

South Asian (SAS) AF: 0.0704 AC: 5245 AN: 74494

European-Finnish (FIN) AF: 0.00510 AC: 195 AN: 38204

Middle Eastern (MID) AF: 0.0511 AC: 254 AN: 4970

European-Non Finnish (NFE) AF: 0.0522 AC: 39696 AN: 761034

Other (OTH) AF: 0.0612 AC: 2882 AN: 47076

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

African (AFR) AF: 0.113 AC: 4665 AN: 41466

American (AMR) AF: 0.0653 AC: 997 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0695 AC: 241 AN: 3466

East Asian (EAS) AF: 0.0656 AC: 339 AN: 5170

South Asian (SAS) AF: 0.0752 AC: 362 AN: 4812

European-Finnish (FIN) AF: 0.00302 AC: 32 AN: 10606

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0469 AC: 3186 AN: 67974

Other (OTH) AF: 0.0710 AC: 150 AN: 2114

Alfa AF: 0.0503 Hom.: 471

Bravo AF: 0.0726

Asia WGS AF: 0.0640 AC: 220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Benign	0.89
PhyloP100		-0.13
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: rs204996; hg19: chr6-32149883; COSMIC: COSV61248179; COSMIC: COSV61248179;