Variant 20-10641432-CAA-CA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000214.3(JAG1):c.2916+27delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4788 hom., cov: 0)

Exomes 𝑓: 0.28 ( 49714 hom. )

Consequence

JAG1
NM_000214.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.173

Variant links:

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]

JAG1 links:

JAG1 (HGNC:):

JAG1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 20-10641432-CA-C is Benign according to our data. Variant chr20-10641432-CA-C is described in ClinVar as [Benign]. Clinvar id is 255555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-10641432-CA-C is described in Lovd as [Benign]. Variant chr20-10641432-CA-C is described in Lovd as [Benign]. Variant chr20-10641432-CA-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAG1	NM_000214.3 linkuse as main transcript	c.2916+27delT		intron_variant		ENST00000254958.10	NP_000205.1	P78504-1Q99740

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAG1	ENST00000254958.10 linkuse as main transcript	c.2916+27delT		intron_variant		1	NM_000214.3	ENSP00000254958.4		P78504-1
JAG1	ENST00000423891.6 linkuse as main transcript	n.2782+27delT		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

34896

AN:

149110

Hom.:

4789

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0883

Gnomad AMI

AF:

0.455

Gnomad AMR

AF:

0.348

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.159

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.252

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.270

GnomAD4 exome

AF:

0.280

AC:

380728

AN:

1360826

Hom.:

49714

Cov.:

AF XY:

0.279

AC XY:

189790

AN XY:

679584

show subpopulations

Gnomad4 AFR exome

AF:

0.0889

Gnomad4 AMR exome

AF:

0.352

Gnomad4 ASJ exome

AF:

0.313

Gnomad4 EAS exome

AF:

0.181

Gnomad4 SAS exome

AF:

0.220

Gnomad4 FIN exome

AF:

0.249

Gnomad4 NFE exome

AF:

0.292

Gnomad4 OTH exome

AF:

0.267

GnomAD4 genome

AF:

0.234

AC:

34920

AN:

149210

Hom.:

4788

Cov.:

AF XY:

0.234

AC XY:

16999

AN XY:

72772

show subpopulations

Gnomad4 AFR

AF:

0.0885

Gnomad4 AMR

AF:

0.349

Gnomad4 ASJ

AF:

0.297

Gnomad4 EAS

AF:

0.159

Gnomad4 SAS

AF:

0.208

Gnomad4 FIN

AF:

0.247

Gnomad4 NFE

AF:

0.294

Gnomad4 OTH

AF:

0.271

Alfa

AF:

0.212

Hom.:

552

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Deafness, congenital heart defects, and posterior embryotoxon

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Alagille syndrome due to a JAG1 point mutation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Tetralogy of Fallot

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over