Variant rs17536052 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000214.3(JAG1):c.388-43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0681 in 1,547,914 control chromosomes in the GnomAD database, including 4,203 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 296 hom., cov: 32)

Exomes 𝑓: 0.070 ( 3907 hom. )

Consequence

JAG1
NM_000214.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.826

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:

Genome browser will be placed here

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 20-10664057-G-A is Benign according to our data. Variant chr20-10664057-G-A is described in ClinVar as [Benign]. Clinvar id is 255559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0762 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.388-43C>T		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.388-43C>T		intron_variant		1	NM_000214.3	ENSP00000254958.4		P78504-1

Frequencies

GnomAD3 genomes

AF:

0.0545

AC:

8288

AN:

152094

Hom.:

296

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0176

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.0795

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0189

Gnomad FIN

AF:

0.0795

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0765

Gnomad OTH

AF:

0.0468

GnomAD3 exomes

AF:

0.0628

AC:

15770

AN:

251170

Hom.:

692

AF XY:

0.0601

AC XY:

8156

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.0169

Gnomad AMR exome

AF:

0.109

Gnomad ASJ exome

AF:

0.0104

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0294

Gnomad FIN exome

AF:

0.0836

Gnomad NFE exome

AF:

0.0754

Gnomad OTH exome

AF:

0.0589

GnomAD4 exome

AF:

0.0695

AC:

97042

AN:

1395702

Hom.:

3907

Cov.:

AF XY:

0.0677

AC XY:

47262

AN XY:

698144

show subpopulations

Gnomad4 AFR exome

AF:

0.0144

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.0115

Gnomad4 EAS exome

AF:

0.000406

Gnomad4 SAS exome

AF:

0.0297

Gnomad4 FIN exome

AF:

0.0868

Gnomad4 NFE exome

AF:

0.0769

Gnomad4 OTH exome

AF:

0.0571

GnomAD4 genome

AF:

0.0545

AC:

8297

AN:

152212

Hom.:

296

Cov.:

AF XY:

0.0537

AC XY:

3995

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0176

Gnomad4 AMR

AF:

0.0799

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0195

Gnomad4 FIN

AF:

0.0795

Gnomad4 NFE

AF:

0.0765

Gnomad4 OTH

AF:

0.0464

Alfa

AF:

0.0608

Hom.:

Bravo

AF:

0.0528

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.24

DANN

Benign

0.77

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