rs6133987

Positions:

• chr20-10669706-C-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409

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=-0.82).
• 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	Protein	UniProt
JAG1	NM_000214.3	c.387+2995G>A		intron_variant		ENST00000254958.10	NP_000205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAG1	ENST00000254958.10	c.387+2995G>A		intron_variant		1	NM_000214.3	ENSP00000254958	P1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26134 AN: 151786 Hom.: 2764 Cov.: 31

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

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

Other links and lift over

dbSNP: rs6133987; hg19: chr20-10650354;