rs6040050

chr20-10640565-C-T

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.3199+218G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,082 control chromosomes in the GnomAD database, including 5,251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (5251 hom., cov: 33)
• Consequence: JAG1 NM_000214.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.163

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=-0.82).
• BP6: Variant 20-10640565-C-T is Benign according to our data. Variant chr20-10640565-C-T is described in ClinVar as [Benign]. Clinvar id is 1296329.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JAG1	NM_000214.3	c.3199+218G>A		intron_variant		ENST00000254958.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAG1	ENST00000254958.10	c.3199+218G>A		intron_variant		1	NM_000214.3	P1
JAG1	ENST00000423891.6	n.3065+218G>A		intron_variant, non_coding_transcript_variant		2
JAG1	ENST00000617357.1	n.494+218G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37529 AN: 151964 Hom.: 5249 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.247 AC: 37561 AN: 152082 Hom.: 5251 Cov.: 33 AF XY: 0.247 AC XY: 18324 AN XY: 74336

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.282

Alfa AF: 0.278 Hom.: 1320

Bravo AF: 0.249

Asia WGS AF: 0.195 AC: 677 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

Jan 25, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.5
Dann	Benign	0.46

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: rs6040050; hg19: chr20-10621213;