rs1635570

chr1-17348106-C-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.1155+58C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 1,122,334 control chromosomes in the GnomAD database, including 1,039 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 0.028 (94 hom., cov: 33)
  • Exomes 𝑓: 0.037 (945 hom.)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326

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=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0285 (4336/152330) while in subpopulation NFE AF= 0.0472 (3214/68038). AF 95% confidence interval is 0.0459. There are 94 homozygotes in gnomad4. There are 2034 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 94 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PADI4	NM_012387.3	c.1155+58C>T		intron_variant		ENST00000375448.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI4	ENST00000375448.4	c.1155+58C>T		intron_variant		1	NM_012387.3	P1
PADI4	ENST00000468945.1	n.272C>T		non_coding_transcript_exon_variant	2/2	2
PADI4	ENST00000487048.5	n.122+58C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0285 AC: 4335 AN: 152212 Hom.: 94 Cov.: 33

Gnomad AFR AF: 0.00743

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0150

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.0367

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0472

Gnomad OTH AF: 0.0182

GnomAD3 exomes AF: 0.0288 AC: 6592 AN: 228496 Hom.: 145 AF XY: 0.0290 AC XY: 3591 AN XY: 123684

Gnomad AFR exome AF: 0.00743

Gnomad AMR exome AF: 0.00933

Gnomad ASJ exome AF: 0.0306

Gnomad EAS exome AF: 0.000300

Gnomad SAS exome AF: 0.00723

Gnomad FIN exome AF: 0.0386

Gnomad NFE exome AF: 0.0470

Gnomad OTH exome AF: 0.0227

GnomAD4 exome AF: 0.0373 AC: 36144 AN: 970004 Hom.: 945 Cov.: 13 AF XY: 0.0365 AC XY: 18296 AN XY: 501608

Gnomad4 AFR exome AF: 0.00743

Gnomad4 AMR exome AF: 0.00953

Gnomad4 ASJ exome AF: 0.0291

Gnomad4 EAS exome AF: 0.000136

Gnomad4 SAS exome AF: 0.00711

Gnomad4 FIN exome AF: 0.0394

Gnomad4 NFE exome AF: 0.0461

Gnomad4 OTH exome AF: 0.0331

GnomAD4 genome AF: 0.0285 AC: 4336 AN: 152330 Hom.: 94 Cov.: 33 AF XY: 0.0273 AC XY: 2034 AN XY: 74486

Gnomad4 AFR AF: 0.00741

Gnomad4 AMR AF: 0.0150

Gnomad4 ASJ AF: 0.0231

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.0367

Gnomad4 NFE AF: 0.0472

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.0376 Hom.: 24

Bravo AF: 0.0257

Asia WGS AF: 0.00577 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.8
Dann	Benign	0.66

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: rs1635570; hg19: chr1-17674601; COSMIC: COSV64924580; COSMIC: COSV64924580;