Variant rs112196689 details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.99

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 20-10641908-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

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAG1	NM_000214.3 link	c.2573-16C>T		intron_variant		ENST00000254958.10	NP_000205.1	P78504-1Q99740

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
JAG1	ENST00000254958.10 link	c.2573-16C>T	intron_variant	1	NM_000214.3	ENSP00000254958.4	P78504-1
JAG1	ENST00000423891.6 link	n.2439-16C>T	intron_variant	2
JAG1	ENST00000617965.2 link	n.3162-16C>T	intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.00563

AC:

857

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0199

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00153

AC:

385

AN:

250962

Hom.:

AF XY:

0.00111

AC XY:

151

AN XY:

135646

show subpopulations

Gnomad AFR exome

AF:

0.0224

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000585

AC:

803

AN:

1372316

Hom.:

Cov.:

AF XY:

0.000491

AC XY:

338

AN XY:

687960

show subpopulations

Gnomad4 AFR exome

AF:

0.0210

Gnomad4 AMR exome

AF:

0.000628

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000237

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.00563

AC:

858

AN:

152282

Hom.:

Cov.:

AF XY:

0.00520

AC XY:

387

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0199

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00266

Hom.:

Bravo

AF:

0.00642

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.026

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