rs748005956
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2
The NM_001370259.2(MEN1):c.655-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000805 in 1,614,104 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001370259.2 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEN1 | NM_001370259.2 | c.655-4del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000450708.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEN1 | ENST00000450708.7 | c.655-4del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001370259.2 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000143 AC: 36AN: 250948Hom.: 0 AF XY: 0.000214 AC XY: 29AN XY: 135670
GnomAD4 exome AF: 0.0000787 AC: 115AN: 1461820Hom.: 0 Cov.: 33 AF XY: 0.000113 AC XY: 82AN XY: 727208
GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74460
ClinVar
Submissions by phenotype
Multiple endocrine neoplasia, type 1 Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Mar 01, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Apr 17, 2023 | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 15, 2019 | This alteration is classified as likely 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. - |
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Dec 07, 2021 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Intronic 1bp del unlikely to impact splicing; ExAC: 0.1% (13/16474) South Asian chromosomes - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 14, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at