5-112839053-TGAA-T
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_000038.6(APC):c.3468_3470delAGA(p.Glu1157del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00083 in 1,614,062 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000038.6 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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APC | ENST00000257430.9 | c.3468_3470delAGA | p.Glu1157del | disruptive_inframe_deletion | Exon 16 of 16 | 5 | NM_000038.6 | ENSP00000257430.4 | ||
ENSG00000258864 | ENST00000520401.1 | n.228+10090_228+10092delAGA | intron_variant | Intron 3 of 7 | 3 | ENSP00000454861.1 |
Frequencies
GnomAD3 genomes AF: 0.00396 AC: 602AN: 152144Hom.: 6 Cov.: 32
GnomAD3 exomes AF: 0.00101 AC: 253AN: 250976Hom.: 1 AF XY: 0.000818 AC XY: 111AN XY: 135644
GnomAD4 exome AF: 0.000506 AC: 740AN: 1461800Hom.: 5 AF XY: 0.000435 AC XY: 316AN XY: 727200
GnomAD4 genome AF: 0.00393 AC: 599AN: 152262Hom.: 6 Cov.: 32 AF XY: 0.00382 AC XY: 284AN XY: 74434
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:6
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This variant is associated with the following publications: (PMID: 22703879, 21488257, 24599579, 27153395, 24345752, 24113346, 29367705) -
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Variant summary: The APC c.3468_3470delAGA (p.Glu1157del) variant causes deletion of a Glutamic acid in a run of 4 repetitive Glutamic acids. This variant was found in 148/121852 control chromosomes (1 homozygote), predominantly observed in the African subpopulation at a frequency of 0.0130777 (133/10170). This frequency is about 183 times the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000714), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. The variant of interest has been reported in patients with familial adenomatous polyposis including co-occurrences with other potentially pathogenic variants (Grandval_2014), supporting for the benign outcome. In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as likely benign/benign. Taken together, this variant is classified as Benign. -
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APC: PM4:Supporting, BS1 -
not specified Benign:6
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Familial adenomatous polyposis 1 Benign:5
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This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. -
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Hereditary cancer-predisposing syndrome Benign:5
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
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Familial multiple polyposis syndrome Benign:1
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APC-Associated Polyposis Disorders Benign:1
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Classic or attenuated familial adenomatous polyposis Benign:1
actually g.112174759_112174761del, c.3468_3470del, p.E1157del was c.3460_3462del, p.1154_1154del -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at