rs112196689
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000214.3(JAG1):c.2573-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,524,598 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0056 ( 11 hom., cov: 33)
Exomes 𝑓: 0.00059 ( 3 hom. )
Consequence
JAG1
NM_000214.3 intron
NM_000214.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.99
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 20-10641908-G-A is Benign according to our data. Variant chr20-10641908-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 255553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-10641908-G-A is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00563 (858/152282) while in subpopulation AFR AF= 0.0199 (827/41570). AF 95% confidence interval is 0.0188. There are 11 homozygotes in gnomad4. There are 387 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 858 AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00563 AC: 857AN: 152168Hom.: 11 Cov.: 33
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GnomAD3 exomes AF: 0.00153 AC: 385AN: 250962Hom.: 1 AF XY: 0.00111 AC XY: 151AN XY: 135646
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GnomAD4 exome AF: 0.000585 AC: 803AN: 1372316Hom.: 3 Cov.: 23 AF XY: 0.000491 AC XY: 338AN XY: 687960
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GnomAD4 genome AF: 0.00563 AC: 858AN: 152282Hom.: 11 Cov.: 33 AF XY: 0.00520 AC XY: 387AN XY: 74468
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jun 17, 2024 | - - |
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 | - | - - |
Alagille syndrome due to a JAG1 point mutation Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 19, 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