rs114048678
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000214.3(JAG1):c.270G>T(p.Gly90Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00439 in 1,613,066 control chromosomes in the GnomAD database, including 223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.023 ( 118 hom., cov: 33)
Exomes 𝑓: 0.0025 ( 105 hom. )
Consequence
JAG1
NM_000214.3 synonymous
NM_000214.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.05
Genes affected
JAG1 (HGNC:6188): (jagged canonical Notch ligand 1) The jagged 1 protein encoded by JAG1 is the human homolog of the Drosophilia jagged protein. Human jagged 1 is the ligand for the receptor notch 1, the latter is involved in signaling processes. Mutations that alter the jagged 1 protein cause Alagille syndrome. Jagged 1 signalling through notch 1 has also been shown to play a role in hematopoiesis. [provided by RefSeq, Nov 2019]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
Variant 20-10672818-C-A is Benign according to our data. Variant chr20-10672818-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 42477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-10672818-C-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-1.05 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0762 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
JAG1 | NM_000214.3 | c.270G>T | p.Gly90Gly | synonymous_variant | 2/26 | ENST00000254958.10 | NP_000205.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
JAG1 | ENST00000254958.10 | c.270G>T | p.Gly90Gly | synonymous_variant | 2/26 | 1 | NM_000214.3 | ENSP00000254958.4 | ||
ENSG00000270792 | ENST00000667822.1 | n.124C>A | non_coding_transcript_exon_variant | 1/2 |
Frequencies
GnomAD3 genomes AF: 0.0229 AC: 3484AN: 152158Hom.: 118 Cov.: 33
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GnomAD3 exomes AF: 0.00622 AC: 1557AN: 250126Hom.: 53 AF XY: 0.00461 AC XY: 625AN XY: 135704
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GnomAD4 exome AF: 0.00245 AC: 3583AN: 1460792Hom.: 105 Cov.: 33 AF XY: 0.00219 AC XY: 1590AN XY: 726716
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GnomAD4 genome AF: 0.0229 AC: 3493AN: 152274Hom.: 118 Cov.: 33 AF XY: 0.0224 AC XY: 1665AN XY: 74470
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:6
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 09, 2011 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 11, 2016 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Isolated Nonsyndromic Congenital Heart Disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Alagille syndrome due to a JAG1 point mutation Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at