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GeneBe

1-17336167-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_012387.3(PADI4):c.349T>C(p.Leu117=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 1,607,184 control chromosomes in the GnomAD database, including 353,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.64 ( 30890 hom., cov: 32)
Exomes 𝑓: 0.66 ( 322229 hom. )

Consequence

PADI4
NM_012387.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 0.249
Variant links:
Genes affected
PADI4 (HGNC:18368): (peptidyl arginine deiminase 4) This gene is a member of a gene family which encodes enzymes responsible for the conversion of arginine residues to citrulline residues. This gene may play a role in granulocyte and macrophage development leading to inflammation and immune response. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-17336167-T-C is Benign according to our data. Variant chr1-17336167-T-C is described in ClinVar as [Benign]. Clinvar id is 972894.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.249 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PADI4NM_012387.3 linkuse as main transcriptc.349T>C p.Leu117= synonymous_variant 4/16 ENST00000375448.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PADI4ENST00000375448.4 linkuse as main transcriptc.349T>C p.Leu117= synonymous_variant 4/161 NM_012387.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.635
AC:
96480
AN:
151842
Hom.:
30885
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.574
Gnomad AMI
AF:
0.703
Gnomad AMR
AF:
0.598
Gnomad ASJ
AF:
0.671
Gnomad EAS
AF:
0.641
Gnomad SAS
AF:
0.587
Gnomad FIN
AF:
0.686
Gnomad MID
AF:
0.621
Gnomad NFE
AF:
0.675
Gnomad OTH
AF:
0.601
GnomAD3 exomes
AF:
0.632
AC:
158374
AN:
250564
Hom.:
50727
AF XY:
0.635
AC XY:
86035
AN XY:
135422
show subpopulations
Gnomad AFR exome
AF:
0.572
Gnomad AMR exome
AF:
0.532
Gnomad ASJ exome
AF:
0.655
Gnomad EAS exome
AF:
0.627
Gnomad SAS exome
AF:
0.573
Gnomad FIN exome
AF:
0.680
Gnomad NFE exome
AF:
0.676
Gnomad OTH exome
AF:
0.637
GnomAD4 exome
AF:
0.663
AC:
964792
AN:
1455226
Hom.:
322229
Cov.:
33
AF XY:
0.661
AC XY:
479011
AN XY:
724410
show subpopulations
Gnomad4 AFR exome
AF:
0.570
Gnomad4 AMR exome
AF:
0.544
Gnomad4 ASJ exome
AF:
0.662
Gnomad4 EAS exome
AF:
0.642
Gnomad4 SAS exome
AF:
0.578
Gnomad4 FIN exome
AF:
0.677
Gnomad4 NFE exome
AF:
0.679
Gnomad4 OTH exome
AF:
0.642
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.635
AC:
96521
AN:
151958
Hom.:
30890
Cov.:
32
AF XY:
0.635
AC XY:
47165
AN XY:
74264
show subpopulations
Gnomad4 AFR
AF:
0.574
Gnomad4 AMR
AF:
0.597
Gnomad4 ASJ
AF:
0.671
Gnomad4 EAS
AF:
0.641
Gnomad4 SAS
AF:
0.585
Gnomad4 FIN
AF:
0.686
Gnomad4 NFE
AF:
0.675
Gnomad4 OTH
AF:
0.594
Alfa
AF:
0.662
Hom.:
65244
Bravo
AF:
0.624
Asia WGS
AF:
0.567
AC:
1971
AN:
3478
EpiCase
AF:
0.665
EpiControl
AF:
0.661

ClinVar

Significance: Benign
Submissions summary: Benign:1Other:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

PADI4-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 17, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Rheumatoid arthritis;C5441745:Abnormal pulmonary interstitial morphology Other:1
association, no assertion criteria providedcase-controlHLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio VillegasFeb 01, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
Cadd
Benign
6.8
Dann
Benign
0.65

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.

Other links and lift over

dbSNP: rs1748033; hg19: chr1-17662662; COSMIC: COSV64923480; COSMIC: COSV64923480; API