3-9890653-G-C

Position:

• chr3-9890653-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032492.4(JAGN1):​c.-70G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 1,461,532 control chromosomes in the GnomAD database, including 335,664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (30760 hom., cov: 31)
  • Exomes 𝑓: 0.68 (304904 hom.)
• Consequence: JAGN1 NM_032492.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0610

Genes affected

JAGN1 (HGNC:26926): (jagunal homolog 1) The protein encoded by this gene is a transmembrane protein. It functions in the early secretory pathway and is necessary for neutrophil differentiation and survival. Mutations in this gene result in severe congenital neutropenia. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 3-9890653-G-C is Benign according to our data. Variant chr3-9890653-G-C is described in ClinVar as [Benign]. Clinvar id is 1223060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JAGN1	NM_032492.4	c.-70G>C		5_prime_UTR_variant	1/2	ENST00000647897.1
JAGN1	NM_001363890.1	c.-338G>C		5_prime_UTR_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAGN1	ENST00000647897.1	c.-70G>C		5_prime_UTR_variant	1/2		NM_032492.4	P1
JAGN1	ENST00000489724.2	c.-70G>C		5_prime_UTR_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95753 AN: 151736 Hom.: 30740 Cov.: 31

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.644

GnomAD4 exome AF: 0.681 AC: 891524 AN: 1309676 Hom.: 304904 Cov.: 18 AF XY: 0.681 AC XY: 440890 AN XY: 647582

Gnomad4 AFR exome AF: 0.494

Gnomad4 AMR exome AF: 0.602

Gnomad4 ASJ exome AF: 0.649

Gnomad4 EAS exome AF: 0.716

Gnomad4 SAS exome AF: 0.651

Gnomad4 FIN exome AF: 0.631

Gnomad4 NFE exome AF: 0.693

Gnomad4 OTH exome AF: 0.678

GnomAD4 genome AF: 0.631 AC: 95813 AN: 151856 Hom.: 30760 Cov.: 31 AF XY: 0.628 AC XY: 46614 AN XY: 74196

Gnomad4 AFR AF: 0.507

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.649

Alfa AF: 0.571 Hom.: 1831

Bravo AF: 0.625

Asia WGS AF: 0.712 AC: 2472 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.2
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs279558; hg19: chr3-9932337; COSMIC: COSV57062656;