rs121909453
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000249.4(MLH1):c.545+20A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000801 in 1,505,092 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000249.4 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00398 AC: 606AN: 152180Hom.: 3 Cov.: 32
GnomAD3 exomes AF: 0.00103 AC: 260AN: 251398Hom.: 2 AF XY: 0.000780 AC XY: 106AN XY: 135886
GnomAD4 exome AF: 0.000442 AC: 598AN: 1352794Hom.: 7 Cov.: 23 AF XY: 0.000380 AC XY: 258AN XY: 679034
GnomAD4 genome AF: 0.00399 AC: 608AN: 152298Hom.: 3 Cov.: 32 AF XY: 0.00384 AC XY: 286AN XY: 74462
ClinVar
Submissions by phenotype
not specified Benign:6
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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. -
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Hereditary cancer-predisposing syndrome Benign:3
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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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not provided Benign:1Other:1
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Colorectal cancer, hereditary nonpolyposis, type 2 Benign:1
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Breast and/or ovarian cancer Benign:1
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Lynch syndrome Benign:1
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Muir-Torré syndrome Benign:1
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Hereditary nonpolyposis colorectal neoplasms Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at