20-10652665-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000214.3(JAG1):c.756-67A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 1,574,848 control chromosomes in the GnomAD database, including 306,720 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.67 (34321 hom., cov: 32)
  • Exomes 𝑓: 0.62 (272399 hom.)
• Consequence: JAG1 NM_000214.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.18

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 20-10652665-T-C is Benign according to our data. Variant chr20-10652665-T-C is described in ClinVar as [Benign]. Clinvar id is 1273216.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JAG1	NM_000214.3	c.756-67A>G		intron_variant		ENST00000254958.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAG1	ENST00000254958.10	c.756-67A>G		intron_variant		1	NM_000214.3	P1
JAG1	ENST00000617965.2	n.58A>G		non_coding_transcript_exon_variant	1/17	5
JAG1	ENST00000423891.6	n.622-67A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101221 AN: 151970 Hom.: 34287 Cov.: 32

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.672

GnomAD4 exome AF: 0.617 AC: 877708 AN: 1422760 Hom.: 272399 Cov.: 22 AF XY: 0.619 AC XY: 439557 AN XY: 709770

Gnomad4 AFR exome AF: 0.809

Gnomad4 AMR exome AF: 0.694

Gnomad4 ASJ exome AF: 0.636

Gnomad4 EAS exome AF: 0.577

Gnomad4 SAS exome AF: 0.700

Gnomad4 FIN exome AF: 0.570

Gnomad4 NFE exome AF: 0.604

Gnomad4 OTH exome AF: 0.623

GnomAD4 genome AF: 0.666 AC: 101313 AN: 152088 Hom.: 34321 Cov.: 32 AF XY: 0.665 AC XY: 49460 AN XY: 74330

Gnomad4 AFR AF: 0.800

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.640

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.699

Gnomad4 FIN AF: 0.565

Gnomad4 NFE AF: 0.607

Gnomad4 OTH AF: 0.671

Alfa AF: 0.617 Hom.: 34072

Bravo AF: 0.677

Asia WGS AF: 0.645 AC: 2247 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.10
Dann	Benign	0.34

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: rs6040055; hg19: chr20-10633313; COSMIC: COSV54756150; COSMIC: COSV54756150;