NM_001136.5:c.992-6G>T

Variant names:

• chr6-32181483-C-A
• rs2071288
• NM_001136.5:c.992-6G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001136.5(AGER):​c.992-6G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AGER NM_001136.5 splice_region, intron
• Scores: Splicing: ADA: 0.00009509
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).

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.992-6G>T		splice_region intron	N/A	NP_001127.1	Q15109-1
	AGER	NM_001206929.2		c.1040-6G>T		splice_region intron	N/A	NP_001193858.1	Q15109-6
	AGER	NM_001206932.2		c.950-6G>T		splice_region 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.992-6G>T		splice_region intron	N/A	ENSP00000364217.4	Q15109-1
	AGER	ENST00000375069.7	TSL:1	c.1040-6G>T		splice_region intron	N/A	ENSP00000364210.4	Q15109-6
	AGER	ENST00000438221.6	TSL:1	c.*29+41G>T		intron	N/A	ENSP00000387887.2	Q15109-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	1.3
DANN	Benign	0.80
PhyloP100		-0.031

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000095
dbscSNV1_RF	Benign	0.0020
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: rs2071288; hg19: chr6-32149260;