6-32182707-T-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001136.5(AGER):c.692-9A>C variant causes a splice polypyrimidine tract, 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.00057 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AGER NM_001136.5 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00004883
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0120

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-32182707-T-G is Benign according to our data. Variant chr6-32182707-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 745864.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGER	NM_001136.5	c.692-9A>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000375076.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGER	ENST00000375076.9	c.692-9A>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001136.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000573 AC: 833 AN: 1453948 Hom.: 0 Cov.: 34 AF XY: 0.000509 AC XY: 368 AN XY: 723504

Gnomad4 AFR exome AF: 0.000570

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.000192

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.000684

Gnomad4 OTH exome AF: 0.000465

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	7.0
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000049
dbscSNV1_RF	Benign	0.020
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: rs1582710968; hg19: chr6-32150484;