Genetic Variant JAG1:c.*1206delT (chr20-10638291-TA-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000214.3(JAG1):c.*1206delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.35 ( 9275 hom., cov: 0)

Exomes 𝑓: 0.43 ( 35 hom. )

Consequence

JAG1
NM_000214.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.21

Publications

1 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 -10 ACMG points.

BP6

Variant 20-10638291-TA-T is Benign according to our data. Variant chr20-10638291-TA-T is described in ClinVar as [Benign]. Clinvar id is 337721.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAG1	NM_000214.3 link	c.*1206delT		3_prime_UTR_variant	Exon 26 of 26	ENST00000254958.10	NP_000205.1	P78504-1Q99740

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAG1	ENST00000254958.10 link	c.*1206delT		3_prime_UTR_variant	Exon 26 of 26	1	NM_000214.3	ENSP00000254958.4		P78504-1
JAG1	ENST00000423891.6 link	n.3550-325delT		intron_variant	Intron 24 of 24	2

Frequencies

GnomAD3 genomes

AF:

0.349

AC:

52342

AN:

149902

Hom.:

9258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.321

Gnomad AMI

AF:

0.521

Gnomad AMR

AF:

0.438

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.185

Gnomad SAS

AF:

0.292

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.353

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.377

GnomAD4 exome

AF:

0.426

AC:

179

AN:

420

Hom.:

Cov.:

AF XY:

0.433

AC XY:

110

AN XY:

254

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.425

AC:

176

AN:

414

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.349

AC:

52402

AN:

150000

Hom.:

9275

Cov.:

AF XY:

0.352

AC XY:

25732

AN XY:

73110

show subpopulations

African (AFR)

AF:

0.321

AC:

13170

AN:

40978

American (AMR)

AF:

0.439

AC:

6610

AN:

15070

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

1015

AN:

3442

East Asian (EAS)

AF:

0.184

AC:

939

AN:

5090

South Asian (SAS)

AF:

0.292

AC:

1381

AN:

4726

European-Finnish (FIN)

AF:

0.372

AC:

3733

AN:

10030

Middle Eastern (MID)

AF:

0.358

AC:

103

AN:

288

European-Non Finnish (NFE)

AF:

0.359

AC:

24192

AN:

67382

Other (OTH)

AF:

0.377

AC:

789

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1723

3445

5168

6890

8613

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.163

Hom.:

331

Bravo

AF:

0.346

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Isolated Nonsyndromic Congenital Heart Disease

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.2

Mutation Taster

=100/0

polymorphism (auto)

(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

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chr20-10638291-TA-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over