20-10638641-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000214.3(JAG1):c.*856_*857insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (6476 hom., cov: 18)
  • Exomes 𝑓: 0.28 (13 hom.)
• Consequence: JAG1 NM_000214.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.73

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 -10 ACMG points.

• BP6: Variant 20-10638641-C-CA is Benign according to our data. Variant chr20-10638641-C-CA is described in ClinVar as [Benign]. Clinvar id is 337729.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JAG1	NM_000214.3	c.*856_*857insT		3_prime_UTR_variant	26/26	ENST00000254958.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAG1	ENST00000254958.10	c.*856_*857insT		3_prime_UTR_variant	26/26	1	NM_000214.3	P1
JAG1	ENST00000423891.6	n.3550-675_3550-674insT		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43532 AN: 151958 Hom.: 6468 Cov.: 18

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.281 AC: 117 AN: 416 Hom.: 13 Cov.: 0 AF XY: 0.268 AC XY: 67 AN XY: 250

Gnomad4 FIN exome AF: 0.279

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.287 AC: 43577 AN: 152076 Hom.: 6476 Cov.: 18 AF XY: 0.287 AC XY: 21310 AN XY: 74342

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.320

Alfa AF: 0.156 Hom.: 293

Bravo AF: 0.292

Asia WGS AF: 0.214 AC: 745 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Isolated Nonsyndromic Congenital Heart Disease Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs3840074; hg19: chr20-10619289;