rs1748034

Positions:

• chr1-17336046-A-C
• chr1-17336046-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.341-113A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 689,166 control chromosomes in the GnomAD database, including 144,211 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 0.65 (32174 hom., cov: 33)
  • Exomes 𝑓: 0.64 (112037 hom.)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PADI4	NM_012387.3	c.341-113A>C		intron_variant		ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4	c.341-113A>C		intron_variant		1	NM_012387.3	ENSP00000364597	P1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98638 AN: 151990 Hom.: 32163 Cov.: 33

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.613

GnomAD4 exome AF: 0.643 AC: 345295 AN: 537058 Hom.: 112037 AF XY: 0.640 AC XY: 182907 AN XY: 285660

Gnomad4 AFR exome AF: 0.608

Gnomad4 AMR exome AF: 0.540

Gnomad4 ASJ exome AF: 0.654

Gnomad4 EAS exome AF: 0.641

Gnomad4 SAS exome AF: 0.568

Gnomad4 FIN exome AF: 0.674

Gnomad4 NFE exome AF: 0.664

Gnomad4 OTH exome AF: 0.636

GnomAD4 genome AF: 0.649 AC: 98690 AN: 152108 Hom.: 32174 Cov.: 33 AF XY: 0.648 AC XY: 48211 AN XY: 74366

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.602

Gnomad4 ASJ AF: 0.672

Gnomad4 EAS AF: 0.641

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.605

Alfa AF: 0.591 Hom.: 1966

Bravo AF: 0.639

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	-0.89
CADD	Benign	3.2
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1748034; hg19: chr1-17662541; COSMIC: COSV64925394; COSMIC: COSV64925394;