rs6133987

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000214.3(JAG1):​c.387+2995G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 151,898 control chromosomes in the GnomAD database, including 2,762 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 2762 hom., cov: 31)

Consequence

JAG1
NM_000214.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.409
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
JAG1NM_000214.3 linkuse as main transcriptc.387+2995G>A intron_variant ENST00000254958.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
JAG1ENST00000254958.10 linkuse as main transcriptc.387+2995G>A intron_variant 1 NM_000214.3 P1P78504-1

Frequencies

GnomAD3 genomes
AF:
0.172
AC:
26134
AN:
151786
Hom.:
2764
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0609
Gnomad AMI
AF:
0.416
Gnomad AMR
AF:
0.210
Gnomad ASJ
AF:
0.294
Gnomad EAS
AF:
0.129
Gnomad SAS
AF:
0.118
Gnomad FIN
AF:
0.164
Gnomad MID
AF:
0.312
Gnomad NFE
AF:
0.228
Gnomad OTH
AF:
0.211
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.172
AC:
26123
AN:
151898
Hom.:
2762
Cov.:
31
AF XY:
0.168
AC XY:
12439
AN XY:
74218
show subpopulations
Gnomad4 AFR
AF:
0.0607
Gnomad4 AMR
AF:
0.209
Gnomad4 ASJ
AF:
0.294
Gnomad4 EAS
AF:
0.129
Gnomad4 SAS
AF:
0.118
Gnomad4 FIN
AF:
0.164
Gnomad4 NFE
AF:
0.228
Gnomad4 OTH
AF:
0.211
Alfa
AF:
0.228
Hom.:
5767
Bravo
AF:
0.175
Asia WGS
AF:
0.131
AC:
454
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
13
DANN
Benign
0.71

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.

Other links and lift over

dbSNP: rs6133987; hg19: chr20-10650354; API