20-10638291-TAAAAA-TAAAAAA

Variant names:

• chr20-10638291-T-TA
• rs34134142
• NM_000214.3:c.*1206dupT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000214.3(JAG1):​c.*1206dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0099 (17 hom., cov: 0)
  • Exomes 𝑓: 0.0071 (0 hom.)
• Consequence: JAG1 NM_000214.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0099 (1487/150148) while in subpopulation SAS AF= 0.022 (104/4734). AF 95% confidence interval is 0.0185. There are 17 homozygotes in gnomad4. There are 720 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1487 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAG1	NM_000214.3	c.*1206dupT		3_prime_UTR_variant	Exon 26 of 26	ENST00000254958.10	NP_000205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAG1	ENST00000254958	c.*1206dupT		3_prime_UTR_variant	Exon 26 of 26	1	NM_000214.3	ENSP00000254958.4
JAG1	ENST00000423891.6	n.3550-325dupT		intron_variant	Intron 24 of 24	2

Frequencies

GnomAD3 genomes AF: 0.00993 AC: 1490 AN: 150048 Hom.: 17 Cov.: 0

Gnomad AFR AF: 0.00264

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.0779

Gnomad EAS AF: 0.00118

Gnomad SAS AF: 0.0224

Gnomad FIN AF: 0.00606

Gnomad MID AF: 0.0128

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.0130

GnomAD4 exome AF: 0.00711 AC: 3 AN: 422 Hom.: 0 Cov.: 0 AF XY: 0.00781 AC XY: 2 AN XY: 256

Gnomad4 FIN exome AF: 0.00721

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00990 AC: 1487 AN: 150148 Hom.: 17 Cov.: 0 AF XY: 0.00984 AC XY: 720 AN XY: 73198

Gnomad4 AFR AF: 0.00263

Gnomad4 AMR AF: 0.0108

Gnomad4 ASJ AF: 0.0779

Gnomad4 EAS AF: 0.00118

Gnomad4 SAS AF: 0.0220

Gnomad4 FIN AF: 0.00606

Gnomad4 NFE AF: 0.0111

Gnomad4 OTH AF: 0.0129

ClinVar

Not reported in ClinVar

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: rs34134142; hg19: chr20-10618939;