Genetic Variant NM_000214.3: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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NM_000214.3:c.*1206delT

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