rs1051121
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1
The NM_002421.4(MMP1):c.831G>A(p.Ala277=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 1,613,932 control chromosomes in the GnomAD database, including 715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.021 ( 49 hom., cov: 33)
Exomes 𝑓: 0.028 ( 666 hom. )
Consequence
MMP1
NM_002421.4 synonymous
NM_002421.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.24
Genes affected
MMP1 (HGNC:7155): (matrix metallopeptidase 1) This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature protease. This secreted protease breaks down the interstitial collagens, including types I, II, and III. The gene is part of a cluster of MMP genes on chromosome 11. Mutations in this gene are associated with chronic obstructive pulmonary disease (COPD). Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
Variant 11-102795242-C-T is Benign according to our data. Variant chr11-102795242-C-T is described in ClinVar as [Benign]. Clinvar id is 403091.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-102795242-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-1.24 with no splicing effect.
BA1
?
GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0587 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MMP1 | NM_002421.4 | c.831G>A | p.Ala277= | synonymous_variant | 6/10 | ENST00000315274.7 | |
WTAPP1 | NR_038390.1 | n.583+18C>T | intron_variant, non_coding_transcript_variant | ||||
MMP1 | NM_001145938.2 | c.633G>A | p.Ala211= | synonymous_variant | 6/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MMP1 | ENST00000315274.7 | c.831G>A | p.Ala277= | synonymous_variant | 6/10 | 1 | NM_002421.4 | P1 | |
WTAPP1 | ENST00000371455.7 | n.325-2782C>T | intron_variant, non_coding_transcript_variant | 4 | |||||
WTAPP1 | ENST00000525739.6 | n.583+18C>T | intron_variant, non_coding_transcript_variant | 2 | |||||
WTAPP1 | ENST00000544704.1 | n.345-2782C>T | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0208 AC: 3162AN: 152146Hom.: 49 Cov.: 33
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GnomAD3 exomes AF: 0.0209 AC: 5230AN: 250400Hom.: 97 AF XY: 0.0221 AC XY: 2990AN XY: 135340
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GnomAD4 exome AF: 0.0277 AC: 40535AN: 1461668Hom.: 666 Cov.: 30 AF XY: 0.0278 AC XY: 20204AN XY: 727140
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 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: Silent variant not in splice consensus - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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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