rs2240336

Positions:

• chr1-17347907-C-T

Variant summary

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

The NM_012387.3(PADI4):​c.1048-34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 1,281,122 control chromosomes in the GnomAD database, including 116,933 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 0.45 (15916 hom., cov: 32)
  • Exomes 𝑓: 0.42 (101017 hom.)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.34

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PADI4	NM_012387.3	c.1048-34C>T		intron_variant		ENST00000375448.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI4	ENST00000375448.4	c.1048-34C>T		intron_variant		1	NM_012387.3	P1
PADI4	ENST00000468945.1	n.107-34C>T		intron_variant, non_coding_transcript_variant		2
PADI4	ENST00000487048.5			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68846 AN: 151888 Hom.: 15905 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.446

GnomAD3 exomes AF: 0.428 AC: 79169 AN: 184870 Hom.: 17295 AF XY: 0.428 AC XY: 42238 AN XY: 98720

Gnomad AFR exome AF: 0.493

Gnomad AMR exome AF: 0.411

Gnomad ASJ exome AF: 0.421

Gnomad EAS exome AF: 0.607

Gnomad SAS exome AF: 0.430

Gnomad FIN exome AF: 0.398

Gnomad NFE exome AF: 0.402

Gnomad OTH exome AF: 0.411

GnomAD4 exome AF: 0.418 AC: 472273 AN: 1129116 Hom.: 101017 Cov.: 14 AF XY: 0.419 AC XY: 235008 AN XY: 560842

Gnomad4 AFR exome AF: 0.488

Gnomad4 AMR exome AF: 0.424

Gnomad4 ASJ exome AF: 0.447

Gnomad4 EAS exome AF: 0.624

Gnomad4 SAS exome AF: 0.435

Gnomad4 FIN exome AF: 0.393

Gnomad4 NFE exome AF: 0.406

Gnomad4 OTH exome AF: 0.431

GnomAD4 genome AF: 0.453 AC: 68898 AN: 152006 Hom.: 15916 Cov.: 32 AF XY: 0.455 AC XY: 33831 AN XY: 74290

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.441

Alfa AF: 0.424 Hom.: 3733

Bravo AF: 0.462

Asia WGS AF: 0.515 AC: 1788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.59
DANN	Benign	0.64

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: rs2240336; hg19: chr1-17674402;