rs6108653

Positions:

• chr20-10649224-T-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_000214.3(JAG1):​c.1349-117A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0898 in 766,934 control chromosomes in the GnomAD database, including 4,795 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (2155 hom., cov: 33)
  • Exomes 𝑓: 0.079 (2640 hom.)
• Consequence: JAG1 NM_000214.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.93

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 20-10649224-T-G is Benign according to our data. Variant chr20-10649224-T-G is described in ClinVar as [Benign]. Clinvar id is 1253419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAG1	NM_000214.3	c.1349-117A>C		intron_variant		ENST00000254958.10	NP_000205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAG1	ENST00000254958.10	c.1349-117A>C		intron_variant		1	NM_000214.3	ENSP00000254958.4

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20352 AN: 152096 Hom.: 2152 Cov.: 33

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0792

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.0479

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0713

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.0789 AC: 48477 AN: 614722 Hom.: 2640 AF XY: 0.0812 AC XY: 26626 AN XY: 327950

Gnomad4 AFR exome AF: 0.287

Gnomad4 AMR exome AF: 0.0445

Gnomad4 ASJ exome AF: 0.0183

Gnomad4 EAS exome AF: 0.0394

Gnomad4 SAS exome AF: 0.155

Gnomad4 FIN exome AF: 0.0695

Gnomad4 NFE exome AF: 0.0686

Gnomad4 OTH exome AF: 0.0794

GnomAD4 genome AF: 0.134 AC: 20364 AN: 152212 Hom.: 2155 Cov.: 33 AF XY: 0.132 AC XY: 9856 AN XY: 74442

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.0791

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.0476

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.0649

Gnomad4 NFE AF: 0.0712

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0854 Hom.: 444

Bravo AF: 0.137

Asia WGS AF: 0.120 AC: 417 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Benign	0.63

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: rs6108653; hg19: chr20-10629872;