NM_012387.3:c.526+751G>A

Variant names:

• chr1-17338906-G-A
• rs1635579
• NM_012387.3:c.526+751G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012387.3(PADI4):​c.526+751G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 152,058 control chromosomes in the GnomAD database, including 31,155 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 0.64 (31155 hom., cov: 33)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.795
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3	c.526+751G>A		intron_variant	Intron 5 of 15	ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4	c.526+751G>A		intron_variant	Intron 5 of 15	1	NM_012387.3	ENSP00000364597.4

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96963 AN: 151940 Hom.: 31150 Cov.: 33

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.605

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.638 AC: 97006 AN: 152058 Hom.: 31155 Cov.: 33 AF XY: 0.638 AC XY: 47407 AN XY: 74300

African (AFR) AF: 0.586 AC: 24315 AN: 41460

American (AMR) AF: 0.598 AC: 9147 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2328 AN: 3468

East Asian (EAS) AF: 0.640 AC: 3302 AN: 5156

South Asian (SAS) AF: 0.584 AC: 2821 AN: 4828

European-Finnish (FIN) AF: 0.684 AC: 7236 AN: 10578

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.673 AC: 45772 AN: 67964

Other (OTH) AF: 0.597 AC: 1262 AN: 2114

Alfa AF: 0.654 Hom.: 4235

Bravo AF: 0.627

Asia WGS AF: 0.566 AC: 1969 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.6
DANN	Benign	0.78
PhyloP100		0.80
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1635579; hg19: chr1-17665401; COSMIC: COSV64923555; COSMIC: COSV64923555;