rs12089685

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_012387.3(PADI4):​c.409-53T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 997,606 control chromosomes in the GnomAD database, including 60 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 0.012 ( 35 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 25 hom. )

Consequence

PADI4
NM_012387.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.82
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0122 (1854/152074) while in subpopulation AFR AF= 0.0414 (1720/41500). AF 95% confidence interval is 0.0398. There are 35 homozygotes in gnomad4. There are 877 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PADI4NM_012387.3 linkuse as main transcriptc.409-53T>C intron_variant ENST00000375448.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PADI4ENST00000375448.4 linkuse as main transcriptc.409-53T>C intron_variant 1 NM_012387.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0122
AC:
1854
AN:
151956
Hom.:
35
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0416
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00584
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000294
Gnomad OTH
AF:
0.0120
GnomAD4 exome
AF:
0.00149
AC:
1257
AN:
845532
Hom.:
25
AF XY:
0.00128
AC XY:
570
AN XY:
443994
show subpopulations
Gnomad4 AFR exome
AF:
0.0389
Gnomad4 AMR exome
AF:
0.00341
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000992
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000230
Gnomad4 OTH exome
AF:
0.00360
GnomAD4 genome
AF:
0.0122
AC:
1854
AN:
152074
Hom.:
35
Cov.:
32
AF XY:
0.0118
AC XY:
877
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.0414
Gnomad4 AMR
AF:
0.00584
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000294
Gnomad4 OTH
AF:
0.0119
Alfa
AF:
0.00860
Hom.:
1
Bravo
AF:
0.0135
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.040
DANN
Benign
0.69

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: rs12089685; hg19: chr1-17664480; API