rs139977567
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBS1BS2_Supporting
The NM_001048174.2(MUTYH):c.264+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000529 in 1,614,156 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001048174.2 intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MUTYH | ENST00000456914.7 | c.264+11G>A | intron_variant | Intron 3 of 15 | 1 | NM_001048174.2 | ENSP00000407590.2 | |||
ENSG00000288208 | ENST00000671898.1 | n.852+11G>A | intron_variant | Intron 7 of 20 | ENSP00000499896.1 |
Frequencies
GnomAD3 genomes AF: 0.000677 AC: 103AN: 152218Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00171 AC: 430AN: 251454Hom.: 9 AF XY: 0.00164 AC XY: 223AN XY: 135900
GnomAD4 exome AF: 0.000515 AC: 753AN: 1461822Hom.: 11 Cov.: 35 AF XY: 0.000494 AC XY: 359AN XY: 727220
GnomAD4 genome AF: 0.000663 AC: 101AN: 152334Hom.: 1 Cov.: 32 AF XY: 0.000779 AC XY: 58AN XY: 74498
ClinVar
Submissions by phenotype
not specified Benign:5
- -
- -
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
- -
- -
Familial adenomatous polyposis 2 Benign:2
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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
- -
Carcinoma of colon Benign:1
The MUTYH c.348+11G>A variant was identified in 1 of 110 proband chromosomes (frequency: 0.001) from individuals or families with lung cancer (Shinmura 2001). The variant was also identified in dbSNP (ID: rs139977567) as With Uncertain significance allele, ClinVar (classified as benign by GeneDx; classified as uncertain significance by Illumina), Clinvitae, Insight Colon Cancer Gene Variant Database, databases. The variant was not identified in UMD-LSDB database. The variant was identified in control databases in 445 (8 homozygous) of 277170 chromosomes at a frequency of 0.0016 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. -
Hereditary cancer-predisposing syndrome Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at