rs765884543
Positions:
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_000214.3(JAG1):c.2724C>T(p.His908=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,616 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: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
JAG1
NM_000214.3 synonymous
NM_000214.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.589
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 -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
Variant 20-10641652-G-A is Benign according to our data. Variant chr20-10641652-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 255554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.589 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JAG1 | NM_000214.3 | c.2724C>T | p.His908= | synonymous_variant | 23/26 | ENST00000254958.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JAG1 | ENST00000254958.10 | c.2724C>T | p.His908= | synonymous_variant | 23/26 | 1 | NM_000214.3 | P1 | |
JAG1 | ENST00000423891.6 | n.2590C>T | non_coding_transcript_exon_variant | 21/25 | 2 | ||||
JAG1 | ENST00000617965.2 | n.3313C>T | non_coding_transcript_exon_variant | 17/17 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 250862Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135648
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461616Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727126
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GnomAD4 genome ? Cov.: 33
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Alagille syndrome due to a JAG1 point mutation Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2023 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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