rs200311847

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000214.3(JAG1):c.886+19A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,613,604 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 7 hom. )

Consequence

JAG1
NM_000214.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.240

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Alagille syndrome due to a JAG1 point mutation
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
Charcot-Marie-Tooth disease, axonal, Type 2HH
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
tetralogy of fallot
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

JAG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 20-10652449-T-A is Benign according to our data. Variant chr20-10652449-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00216 (329/152250) while in subpopulation NFE AF = 0.00398 (271/68006). AF 95% confidence interval is 0.00359. There are 1 homozygotes in GnomAd4. There are 141 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 329 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAG1	NM_000214.3 link	c.886+19A>T		intron_variant	Intron 6 of 25	ENST00000254958.10	NP_000205.1	P78504-1Q99740

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
JAG1	ENST00000254958.10 link	c.886+19A>T	intron_variant	Intron 6 of 25	1	NM_000214.3	ENSP00000254958.4	P78504-1
JAG1	ENST00000423891.6 link	n.752+19A>T	intron_variant	Intron 4 of 24	2
JAG1	ENST00000617965.2 link	n.255+19A>T	intron_variant	Intron 1 of 16	5

Frequencies

GnomAD3 genomes

AF:

0.00216

AC:

329

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00398

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00213

AC:

535

AN:

251304

AF XY:

0.00226

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000954

Gnomad ASJ exome

AF:

0.00258

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000693

Gnomad NFE exome

AF:

0.00370

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00276

AC:

4027

AN:

1461354

Hom.:

Cov.:

AF XY:

0.00265

AC XY:

1925

AN XY:

726980

show subpopulations

African (AFR)

AF:

0.000478

AC:

AN:

33454

American (AMR)

AF:

0.000894

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00207

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.000464

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.000843

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.000355

AC:

AN:

5632

European-Non Finnish (NFE)

AF:

0.00334

AC:

3711

AN:

1111746

Other (OTH)

AF:

0.00197

AC:

119

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

193

386

579

772

965

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

248

372

496

620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00216

AC:

329

AN:

152250

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

141

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.000674

AC:

AN:

41564

American (AMR)

AF:

0.000980

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00398

AC:

271

AN:

68006

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00316

Hom.:

Bravo

AF:

0.00194

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Alagille syndrome due to a JAG1 point mutation

Benign:1

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.29

(source)

DANN

Benign

0.43

PhyloP100

-0.24

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over