rs373534760
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_003183.6(ADAM17):c.354C>T(p.His118=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,774 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
ADAM17
NM_003183.6 synonymous
NM_003183.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.521
Genes affected
ADAM17 (HGNC:195): (ADAM metallopeptidase domain 17) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biologic processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The encoded preproprotein is proteolytically processed to generate the mature protease. The encoded protease functions in the ectodomain shedding of tumor necrosis factor-alpha, in which soluble tumor necrosis factor-alpha is released from the membrane-bound precursor. This protease also functions in the processing of numerous other substrates, including cell adhesion proteins, cytokine and growth factor receptors and epidermal growth factor (EGF) receptor ligands, and plays a prominent role in the activation of the Notch signaling pathway. Elevated expression of this gene has been observed in specific cell types derived from psoriasis, rheumatoid arthritis, multiple sclerosis and Crohn's disease patients, suggesting that the encoded protein may play a role in autoimmune disease. Additionally, this protease may play a role in viral infection through its cleavage of ACE2, the cellular receptor for SARS-CoV and SARS-CoV-2. [provided by RefSeq, Aug 2020]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 2-9536705-G-A is Benign according to our data. Variant chr2-9536705-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 539954.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.521 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAM17 | NM_003183.6 | c.354C>T | p.His118= | synonymous_variant | 3/19 | ENST00000310823.8 | |
ADAM17 | XM_047445610.1 | c.261C>T | p.His87= | synonymous_variant | 4/20 | ||
ADAM17 | NM_001382777.1 | c.-327C>T | 5_prime_UTR_variant | 3/19 | |||
ADAM17 | NM_001382778.1 | c.-569C>T | 5_prime_UTR_variant | 3/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAM17 | ENST00000310823.8 | c.354C>T | p.His118= | synonymous_variant | 3/19 | 1 | NM_003183.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152086Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251372Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135850
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461688Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13AN XY: 727144
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152086Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74270
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inflammatory skin and bowel disease, neonatal, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 22, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at