NM_012387.3:c.93-143C>T

Variant names:

• chr1-17330826-C-T
• rs1635598
• NM_012387.3:c.93-143C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_012387.3(PADI4):​c.93-143C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 576,050 control chromosomes in the GnomAD database, including 505 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 0.031 (96 hom., cov: 33)
  • Exomes 𝑓: 0.039 (409 hom.)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0314 (4777/152294) while in subpopulation NFE AF= 0.0473 (3217/68010). AF 95% confidence interval is 0.0459. There are 96 homozygotes in gnomad4. There are 2283 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 96 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3	c.93-143C>T		intron_variant	Intron 1 of 15	ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4	c.93-143C>T		intron_variant	Intron 1 of 15	1	NM_012387.3	ENSP00000364597.4
PADI4	ENST00000375453.5	c.93-143C>T		intron_variant	Intron 1 of 3	2		ENSP00000364602.1

Frequencies

GnomAD3 genomes AF: 0.0314 AC: 4774 AN: 152176 Hom.: 96 Cov.: 33

Gnomad AFR AF: 0.0152

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0256

Gnomad FIN AF: 0.0367

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0473

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.0387 AC: 16391 AN: 423756 Hom.: 409 AF XY: 0.0379 AC XY: 8405 AN XY: 221494

Gnomad4 AFR exome AF: 0.0153

Gnomad4 AMR exome AF: 0.0140

Gnomad4 ASJ exome AF: 0.0284

Gnomad4 EAS exome AF: 0.000447

Gnomad4 SAS exome AF: 0.0196

Gnomad4 FIN exome AF: 0.0380

Gnomad4 NFE exome AF: 0.0475

Gnomad4 OTH exome AF: 0.0341

GnomAD4 genome AF: 0.0314 AC: 4777 AN: 152294 Hom.: 96 Cov.: 33 AF XY: 0.0307 AC XY: 2283 AN XY: 74468

Gnomad4 AFR AF: 0.0152

Gnomad4 AMR AF: 0.0155

Gnomad4 ASJ AF: 0.0233

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0257

Gnomad4 FIN AF: 0.0367

Gnomad4 NFE AF: 0.0473

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0170 Hom.: 14

Bravo AF: 0.0286

Asia WGS AF: 0.0170 AC: 59 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.83
DANN	Benign	0.48

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: rs1635598; hg19: chr1-17657321;