rs12746451

Positions:

• chr1-17348326-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.1155+278C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0841 in 283,278 control chromosomes in the GnomAD database, including 1,243 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 0.091 (808 hom., cov: 33)
  • Exomes 𝑓: 0.076 (435 hom.)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.995

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PADI4	NM_012387.3	c.1155+278C>T		intron_variant		ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4	c.1155+278C>T		intron_variant		1	NM_012387.3	ENSP00000364597	P1
PADI4	ENST00000487048.5	n.122+278C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0906 AC: 13779 AN: 152128 Hom.: 804 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0593

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.0488

Gnomad SAS AF: 0.0318

Gnomad FIN AF: 0.0714

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0679

Gnomad OTH AF: 0.0876

GnomAD4 exome AF: 0.0764 AC: 10010 AN: 131032 Hom.: 435 AF XY: 0.0752 AC XY: 5082 AN XY: 67596

Gnomad4 AFR exome AF: 0.185

Gnomad4 AMR exome AF: 0.0514

Gnomad4 ASJ exome AF: 0.0539

Gnomad4 EAS exome AF: 0.0599

Gnomad4 SAS exome AF: 0.0458

Gnomad4 FIN exome AF: 0.0748

Gnomad4 NFE exome AF: 0.0769

Gnomad4 OTH exome AF: 0.0822

GnomAD4 genome AF: 0.0907 AC: 13815 AN: 152246 Hom.: 808 Cov.: 33 AF XY: 0.0890 AC XY: 6622 AN XY: 74444

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0592

Gnomad4 ASJ AF: 0.0487

Gnomad4 EAS AF: 0.0485

Gnomad4 SAS AF: 0.0319

Gnomad4 FIN AF: 0.0714

Gnomad4 NFE AF: 0.0680

Gnomad4 OTH AF: 0.0876

Alfa AF: 0.0689 Hom.: 382

Bravo AF: 0.0923

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.20
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12746451; hg19: chr1-17674821;