NM_001370259.2:c.1049+9C>T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001370259.2(MEN1):c.1049+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000991 in 1,613,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001370259.2 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MEN1 | NM_001370259.2 | c.1049+9C>T | intron_variant | Intron 7 of 9 | ENST00000450708.7 | NP_001357188.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000473 AC: 72AN: 152180Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000410 AC: 103AN: 251372Hom.: 0 AF XY: 0.000390 AC XY: 53AN XY: 135866
GnomAD4 exome AF: 0.00105 AC: 1528AN: 1461762Hom.: 0 Cov.: 32 AF XY: 0.000978 AC XY: 711AN XY: 727202
GnomAD4 genome AF: 0.000473 AC: 72AN: 152180Hom.: 0 Cov.: 33 AF XY: 0.000444 AC XY: 33AN XY: 74328
ClinVar
Submissions by phenotype
not specified Benign:3
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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. -
Variant summary: MEN1 c.1049+9C>T alters a non-conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00041 in 251372 control chromosomes (gnomAD). The observed variant frequency is approximately 20 fold of the estimated maximal expected allele frequency for a pathogenic variant in MEN1 causing Multiple Endocrine Neoplasia Type 1 phenotype (2.1e-05), strongly suggesting that the variant is benign. The following publication has been ascertained in the context of this evaluation (PMID: 37484956). ClinVar contains an entry for this variant (Variation ID: 36519). Based on the evidence outlined above, the variant was classified as benign. -
not provided Benign:3
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MEN1: BS2 -
Multiple endocrine neoplasia, type 1 Benign:2
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -
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Hereditary cancer-predisposing syndrome Benign:2
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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. -
Hyperparathyroidism Uncertain:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at