1-17338275-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012387.3(PADI4):c.526+120A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 678,678 control chromosomes in the GnomAD database, including 143,505 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 0.64 (31618 hom., cov: 32)
  • Exomes 𝑓: 0.65 (111887 hom.)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PADI4	NM_012387.3	c.526+120A>G		intron_variant		ENST00000375448.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI4	ENST00000375448.4	c.526+120A>G		intron_variant		1	NM_012387.3	P1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97782 AN: 151976 Hom.: 31607 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.608

GnomAD4 exome AF: 0.649 AC: 341548 AN: 526584 Hom.: 111887 AF XY: 0.647 AC XY: 184864 AN XY: 285748

Gnomad4 AFR exome AF: 0.601

Gnomad4 AMR exome AF: 0.544

Gnomad4 ASJ exome AF: 0.663

Gnomad4 EAS exome AF: 0.642

Gnomad4 SAS exome AF: 0.575

Gnomad4 FIN exome AF: 0.676

Gnomad4 NFE exome AF: 0.675

Gnomad4 OTH exome AF: 0.643

GnomAD4 genome AF: 0.643 AC: 97834 AN: 152094 Hom.: 31618 Cov.: 32 AF XY: 0.643 AC XY: 47810 AN XY: 74362

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.641

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.674

Gnomad4 OTH AF: 0.600

Alfa AF: 0.649 Hom.: 13588

Bravo AF: 0.633

Asia WGS AF: 0.569 AC: 1977 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	5.8
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs1635586; hg19: chr1-17664770; COSMIC: COSV64923530; COSMIC: COSV64923530;