rs180737290
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001370259.2(MEN1):c.654+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000986 in 1,613,140 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000084 ( 2 hom. )
Consequence
MEN1
NM_001370259.2 intron
NM_001370259.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.133
Genes affected
MEN1 (HGNC:7010): (menin 1) This gene encodes menin, a tumor suppressor associated with a syndrome known as multiple endocrine neoplasia type 1. Menin is a scaffold protein that functions in histone modification and epigenetic gene regulation. It is thought to regulate several pathways and processes by altering chromatin structure through the modification of histones. [provided by RefSeq, May 2019]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 11-64807873-G-A is Benign according to our data. Variant chr11-64807873-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 36535.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Uncertain_significance=1, Likely_benign=1}.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000243 (37/152226) while in subpopulation EAS AF= 0.00714 (37/5182). AF 95% confidence interval is 0.00532. There are 0 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 37 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEN1 | NM_001370259.2 | c.654+18C>T | intron_variant | ENST00000450708.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEN1 | ENST00000450708.7 | c.654+18C>T | intron_variant | 5 | NM_001370259.2 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000243 AC: 37AN: 152108Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000360 AC: 90AN: 250208Hom.: 0 AF XY: 0.000354 AC XY: 48AN XY: 135436
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GnomAD4 exome AF: 0.0000835 AC: 122AN: 1460914Hom.: 2 Cov.: 33 AF XY: 0.0000743 AC XY: 54AN XY: 726814
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Multiple endocrine neoplasia, type 1 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing;curation | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 18, 2011 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 06, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 15, 2017 | 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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at