rs6514116

Variant names:

• chr20-10657920-G-A
• rs6514116
• NM_000214.3:c.694+548C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-10657920-G-A
• chr20-10657920-G-C
• chr20-10657920-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000214.3(JAG1):​c.694+548C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,046 control chromosomes in the GnomAD database, including 19,283 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 0.50 (19283 hom., cov: 33)
• Consequence: JAG1 NM_000214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• Alagille syndrome due to a JAG1 point mutation

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• Charcot-Marie-Tooth disease, axonal, Type 2HH

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• tetralogy of fallot

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAG1	NM_000214.3	c.694+548C>T		intron_variant	Intron 4 of 25	ENST00000254958.10	NP_000205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAG1	ENST00000254958.10	c.694+548C>T		intron_variant	Intron 4 of 25	1	NM_000214.3	ENSP00000254958.4
JAG1	ENST00000423891.6	n.560+548C>T		intron_variant	Intron 2 of 24	2

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76239 AN: 151930 Hom.: 19248 Cov.: 33

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.502 AC: 76328 AN: 152046 Hom.: 19283 Cov.: 33 AF XY: 0.508 AC XY: 37759 AN XY: 74326

African (AFR) AF: 0.490 AC: 20321 AN: 41436

American (AMR) AF: 0.561 AC: 8579 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1778 AN: 3468

East Asian (EAS) AF: 0.677 AC: 3504 AN: 5176

South Asian (SAS) AF: 0.602 AC: 2898 AN: 4814

European-Finnish (FIN) AF: 0.526 AC: 5562 AN: 10582

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 32017 AN: 67962

Other (OTH) AF: 0.511 AC: 1081 AN: 2116

Alfa AF: 0.483 Hom.: 6822

Bravo AF: 0.502

Asia WGS AF: 0.630 AC: 2191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.67
PhyloP100		-0.042
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6514116; hg19: chr20-10638568;