1-17336144-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_012387.3(PADI4):c.341-15T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 1,592,118 control chromosomes in the GnomAD database, including 263,124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.54 (22893 hom., cov: 32)
  • Exomes 𝑓: 0.58 (240231 hom.)
• Consequence: PADI4 NM_012387.3 splice_polypyrimidine_tract, intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.0470

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PADI4	NM_012387.3	c.341-15T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000375448.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI4	ENST00000375448.4	c.341-15T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_012387.3	P1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82805 AN: 151860 Hom.: 22905 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.528

GnomAD3 exomes AF: 0.559 AC: 139599 AN: 249740 Hom.: 39378 AF XY: 0.563 AC XY: 76000 AN XY: 134958

Gnomad AFR exome AF: 0.454

Gnomad AMR exome AF: 0.504

Gnomad ASJ exome AF: 0.596

Gnomad EAS exome AF: 0.578

Gnomad SAS exome AF: 0.528

Gnomad FIN exome AF: 0.589

Gnomad NFE exome AF: 0.586

Gnomad OTH exome AF: 0.573

GnomAD4 exome AF: 0.575 AC: 828470 AN: 1440142 Hom.: 240231 Cov.: 28 AF XY: 0.575 AC XY: 412839 AN XY: 717856

Gnomad4 AFR exome AF: 0.452

Gnomad4 AMR exome AF: 0.513

Gnomad4 ASJ exome AF: 0.604

Gnomad4 EAS exome AF: 0.593

Gnomad4 SAS exome AF: 0.532

Gnomad4 FIN exome AF: 0.587

Gnomad4 NFE exome AF: 0.584

Gnomad4 OTH exome AF: 0.557

GnomAD4 genome AF: 0.545 AC: 82823 AN: 151976 Hom.: 22893 Cov.: 32 AF XY: 0.546 AC XY: 40531 AN XY: 74284

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.537

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.521

Alfa AF: 0.570 Hom.: 4632

Bravo AF: 0.537

Asia WGS AF: 0.484 AC: 1683 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Rheumatoid arthritis Other:1

association, no assertion criteria provided

case-control

Department of Zoology, University of the Punjab, Lahore

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	7.5
Dann	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.42		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2240340; hg19: chr1-17662639; COSMIC: COSV64923475; COSMIC: COSV64923475;