rs6683201

chr1-17354782-T-Cchr1-17354782-T-G

Variant summary

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

The NM_012387.3(PADI4):c.1310+95T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 1,212,040 control chromosomes in the GnomAD database, including 310,008 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 0.75 (43774 hom., cov: 32)
  • Exomes 𝑓: 0.71 (266234 hom.)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PADI4	NM_012387.3	c.1310+95T>C		intron_variant		ENST00000375448.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI4	ENST00000375448.4	c.1310+95T>C		intron_variant		1	NM_012387.3	P1
PADI4	ENST00000467001.1	n.211+95T>C		intron_variant, non_coding_transcript_variant		5
PADI4	ENST00000487048.5	n.277+95T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114201 AN: 151990 Hom.: 43725 Cov.: 32

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.793

GnomAD4 exome AF: 0.707 AC: 749138 AN: 1059932 Hom.: 266234 AF XY: 0.707 AC XY: 371798 AN XY: 525786

Gnomad4 AFR exome AF: 0.909

Gnomad4 AMR exome AF: 0.679

Gnomad4 ASJ exome AF: 0.828

Gnomad4 EAS exome AF: 0.792

Gnomad4 SAS exome AF: 0.719

Gnomad4 FIN exome AF: 0.623

Gnomad4 NFE exome AF: 0.696

Gnomad4 OTH exome AF: 0.725

GnomAD4 genome AF: 0.751 AC: 114303 AN: 152108 Hom.: 43774 Cov.: 32 AF XY: 0.743 AC XY: 55260 AN XY: 74370

Gnomad4 AFR AF: 0.894

Gnomad4 AMR AF: 0.695

Gnomad4 ASJ AF: 0.825

Gnomad4 EAS AF: 0.773

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.792

Alfa AF: 0.720 Hom.: 53896

Bravo AF: 0.766

Asia WGS AF: 0.736 AC: 2558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.6
Dann	Benign	0.31

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: rs6683201; hg19: chr1-17681277; COSMIC: COSV64923587;