rs765442930
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2
The NM_000214.3(JAG1):c.105C>T(p.Phe35=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000193 in 1,609,606 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 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
JAG1
NM_000214.3 synonymous
NM_000214.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.20
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
?
Variant 20-10672983-G-A is Benign according to our data. Variant chr20-10672983-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 414161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-10672983-G-A is described in Lovd as [Benign].
BS2
?
High AC in GnomAdExome at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JAG1 | NM_000214.3 | c.105C>T | p.Phe35= | synonymous_variant | 2/26 | ENST00000254958.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JAG1 | ENST00000254958.10 | c.105C>T | p.Phe35= | synonymous_variant | 2/26 | 1 | NM_000214.3 | P1 | |
ENST00000605292.5 | n.56G>A | non_coding_transcript_exon_variant | 1/5 | 3 | |||||
ENST00000667822.1 | n.289G>A | non_coding_transcript_exon_variant | 1/2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152114Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000405 AC: 10AN: 246630Hom.: 0 AF XY: 0.0000372 AC XY: 5AN XY: 134238
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GnomAD4 exome AF: 0.0000185 AC: 27AN: 1457492Hom.: 0 Cov.: 34 AF XY: 0.0000165 AC XY: 12AN XY: 725268
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152114Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74290
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Alagille syndrome due to a JAG1 point mutation Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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Name
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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