chr5-112835173-T-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000038.6(APC):c.1958+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 1,602,474 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000038.6 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 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.1958+8T>C | splice_region_variant, intron_variant | Intron 15 of 15 | 5 | NM_000038.6 | ENSP00000257430.4 | |||
ENSG00000258864 | ENST00000520401.1 | n.228+6201T>C | intron_variant | Intron 3 of 7 | 3 | ENSP00000454861.1 |
Frequencies
GnomAD3 genomes AF: 0.00578 AC: 880AN: 152190Hom.: 19 Cov.: 32
GnomAD3 exomes AF: 0.00797 AC: 1911AN: 239770Hom.: 68 AF XY: 0.00748 AC XY: 971AN XY: 129772
GnomAD4 exome AF: 0.00343 AC: 4972AN: 1450166Hom.: 109 Cov.: 28 AF XY: 0.00346 AC XY: 2500AN XY: 721684
GnomAD4 genome AF: 0.00582 AC: 886AN: 152308Hom.: 19 Cov.: 32 AF XY: 0.00602 AC XY: 448AN XY: 74468
ClinVar
Submissions by phenotype
not specified Benign:8
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Familial adenomatous polyposis 1 Benign:3
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This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. 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:3
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not provided Benign:2
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APC-Associated Polyposis Disorders Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Carcinoma of colon Benign:1
The c.1958+8T>C variant has been reported once in the InSiGHT database in an individual with familial adenomatous polyposis. It is listed in the dbSNP database (rs#:62626346) and reported from the 1000 genomes project (frequency: 0.026) and in a Chinese and Japanese cohort (frequency: 0.067) as well as the exome variant server as a low frequency variant increasing the likelihood this variant does not have clinical significance. The variant is located in the 5' splice region but does not affect the highly conserved +1 and +2 positions. In summary, based on above information this variant meets our laboratory's criteria to be classified benign. -
Familial colorectal cancer Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at