rs6133986

chr20-10665125-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000214.3(JAG1):c.388-1111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,118 control chromosomes in the GnomAD database, including 852 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 0.10 (852 hom., cov: 33)
• Consequence: JAG1 NM_000214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JAG1	NM_000214.3	c.388-1111C>T		intron_variant		ENST00000254958.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAG1	ENST00000254958.10	c.388-1111C>T		intron_variant		1	NM_000214.3	P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15418 AN: 152000 Hom.: 852 Cov.: 33

Gnomad AFR AF: 0.0864

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0830

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0250

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.110

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.101 AC: 15427 AN: 152118 Hom.: 852 Cov.: 33 AF XY: 0.102 AC XY: 7561 AN XY: 74392

Gnomad4 AFR AF: 0.0863

Gnomad4 AMR AF: 0.0829

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.0247

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.111

Alfa AF: 0.107 Hom.: 211

Bravo AF: 0.0986

Asia WGS AF: 0.0670 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.6
Dann	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs6133986; hg19: chr20-10645773;