rs201234393
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000214.3(JAG1):c.2559C>T(p.Ala853=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00068 in 1,607,866 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00050 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00070 ( 21 hom. )
Consequence
JAG1
NM_000214.3 synonymous
NM_000214.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.126
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
Variant 20-10642501-G-A is Benign according to our data. Variant chr20-10642501-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 167201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.126 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000499 (76/152288) while in subpopulation SAS AF= 0.0155 (75/4828). AF 95% confidence interval is 0.0127. There are 1 homozygotes in gnomad4. There are 58 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 76 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JAG1 | NM_000214.3 | c.2559C>T | p.Ala853= | synonymous_variant | 21/26 | ENST00000254958.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JAG1 | ENST00000254958.10 | c.2559C>T | p.Ala853= | synonymous_variant | 21/26 | 1 | NM_000214.3 | P1 | |
JAG1 | ENST00000423891.6 | n.2425C>T | non_coding_transcript_exon_variant | 19/25 | 2 | ||||
JAG1 | ENST00000617965.2 | n.3148C>T | non_coding_transcript_exon_variant | 15/17 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000506 AC: 77AN: 152170Hom.: 1 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
77
AN:
152170
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00158 AC: 396AN: 251314Hom.: 6 AF XY: 0.00216 AC XY: 294AN XY: 135826
GnomAD3 exomes
AF:
AC:
396
AN:
251314
Hom.:
AF XY:
AC XY:
294
AN XY:
135826
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000699 AC: 1017AN: 1455578Hom.: 21 Cov.: 30 AF XY: 0.00103 AC XY: 749AN XY: 724502
GnomAD4 exome
AF:
AC:
1017
AN:
1455578
Hom.:
Cov.:
30
AF XY:
AC XY:
749
AN XY:
724502
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000499 AC: 76AN: 152288Hom.: 1 Cov.: 33 AF XY: 0.000779 AC XY: 58AN XY: 74476
GnomAD4 genome
?
AF:
AC:
76
AN:
152288
Hom.:
Cov.:
33
AF XY:
AC XY:
58
AN XY:
74476
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
21
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 19, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | JAG1: BP4, BP7, BS1, BS2 - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 04, 2017 | - - |
Alagille syndrome due to a JAG1 point mutation Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Tetralogy of Fallot;C1866053:Deafness, congenital heart defects, and posterior embryotoxon;C1956125:Alagille syndrome due to a JAG1 point mutation;C5562003:Charcot-Marie-Tooth disease, axonal, Type 2HH Benign:1
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 20, 2021 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 29, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at