Variant rs138937423 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_032492.4(JAGN1):c.21G>C(p.Pro7Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00425 in 1,609,170 control chromosomes in the GnomAD database, including 218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 17 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 201 hom. )

Consequence

JAGN1
NM_032492.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.508

Variant links:

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]

JAGN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 3-9890743-G-C is Benign according to our data. Variant chr3-9890743-G-C is described in ClinVar as [Benign]. Clinvar id is 475245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.508 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAGN1	NM_032492.4 link	c.21G>C	p.Pro7Pro	synonymous_variant	Exon 1 of 2	ENST00000647897.1	NP_115881.3	Q8N5M9
JAGN1	NM_001363890.1 link	c.-248G>C		5_prime_UTR_variant	Exon 1 of 2		NP_001350819.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAGN1	ENST00000647897.1 link	c.21G>C	p.Pro7Pro	synonymous_variant	Exon 1 of 2		NM_032492.4	ENSP00000496942.1		Q8N5M9
JAGN1	ENST00000489724.2 link	c.21G>C	p.Pro7Pro	synonymous_variant	Exon 1 of 2	3		ENSP00000497724.1		A0A3B3ITE9

Frequencies

GnomAD3 genomes

AF:

0.00477

AC:

726

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0174

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00654

Gnomad SAS

AF:

0.0598

Gnomad FIN

AF:

0.00678

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00985

AC:

2332

AN:

236842

Hom.:

AF XY:

0.0111

AC XY:

1432

AN XY:

128988

show subpopulations

Gnomad AFR exome

AF:

0.000542

Gnomad AMR exome

AF:

0.0138

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00522

Gnomad SAS exome

AF:

0.0530

Gnomad FIN exome

AF:

0.00608

Gnomad NFE exome

AF:

0.000639

Gnomad OTH exome

AF:

0.00511

GnomAD4 exome

AF:

0.00420

AC:

6117

AN:

1456816

Hom.:

201

Cov.:

AF XY:

0.00552

AC XY:

3998

AN XY:

724352

show subpopulations

Gnomad4 AFR exome

AF:

0.000419

Gnomad4 AMR exome

AF:

0.0131

Gnomad4 ASJ exome

AF:

0.0000386

Gnomad4 EAS exome

AF:

0.00251

Gnomad4 SAS exome

AF:

0.0520

Gnomad4 FIN exome

AF:

0.00577

Gnomad4 NFE exome

AF:

0.000278

Gnomad4 OTH exome

AF:

0.00625

GnomAD4 genome

AF:

0.00479

AC:

730

AN:

152354

Hom.:

Cov.:

AF XY:

0.00644

AC XY:

480

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.0174

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00656

Gnomad4 SAS

AF:

0.0600

Gnomad4 FIN

AF:

0.00678

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00114

Hom.:

Bravo

AF:

0.00333

Asia WGS

AF:

0.0350

AC:

123

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal recessive severe congenital neutropenia due to JAGN1 deficiency

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

May 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.84

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over