chr20-10641853-G-C
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1
The NM_000214.3(JAG1):āc.2612C>Gā(p.Pro871Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0657 in 1,613,100 control chromosomes in the GnomAD database, including 4,249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P871T) has been classified as Uncertain significance.
Frequency
Consequence
NM_000214.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JAG1 | NM_000214.3 | c.2612C>G | p.Pro871Arg | missense_variant | 22/26 | ENST00000254958.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JAG1 | ENST00000254958.10 | c.2612C>G | p.Pro871Arg | missense_variant | 22/26 | 1 | NM_000214.3 | P1 | |
JAG1 | ENST00000423891.6 | n.2478C>G | non_coding_transcript_exon_variant | 20/25 | 2 | ||||
JAG1 | ENST00000617965.2 | n.3201C>G | non_coding_transcript_exon_variant | 16/17 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0508 AC: 7726AN: 152166Hom.: 255 Cov.: 33
GnomAD3 exomes AF: 0.0634 AC: 15942AN: 251368Hom.: 746 AF XY: 0.0693 AC XY: 9418AN XY: 135848
GnomAD4 exome AF: 0.0673 AC: 98286AN: 1460816Hom.: 3997 Cov.: 32 AF XY: 0.0694 AC XY: 50428AN XY: 726824
GnomAD4 genome AF: 0.0508 AC: 7732AN: 152284Hom.: 252 Cov.: 33 AF XY: 0.0515 AC XY: 3832AN XY: 74458
ClinVar
Submissions by phenotype
not specified Benign:8
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 03, 2010 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 05, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 10, 2023 | - - |
Isolated Nonsyndromic Congenital Heart Disease Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Alagille syndrome due to a JAG1 point mutation Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 29, 2015 | This alteration is classified as 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at