rs16825533

Variant names:

• chr1-17339386-A-G
• rs16825533
• NM_012387.3:c.527-302A>G

Variant summary

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

The NM_012387.3(PADI4):​c.527-302A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0417 in 152,300 control chromosomes in the GnomAD database, including 189 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 0.042 (189 hom., cov: 32)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3	c.527-302A>G		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.527-302A>G		intron_variant	Intron 5 of 15	1	NM_012387.3	ENSP00000364597.4

Frequencies

GnomAD3 genomes AF: 0.0416 AC: 6335 AN: 152182 Hom.: 184 Cov.: 32

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0304

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0799

Gnomad FIN AF: 0.0529

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.0547

Gnomad OTH AF: 0.0460

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

GnomAD4 genome AF: 0.0417 AC: 6354 AN: 152300 Hom.: 189 Cov.: 32 AF XY: 0.0422 AC XY: 3146 AN XY: 74464

African (AFR) AF: 0.0105 AC: 437 AN: 41564

American (AMR) AF: 0.0304 AC: 465 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 83 AN: 3470

East Asian (EAS) AF: 0.104 AC: 538 AN: 5182

South Asian (SAS) AF: 0.0816 AC: 394 AN: 4830

European-Finnish (FIN) AF: 0.0529 AC: 562 AN: 10616

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.0547 AC: 3718 AN: 68024

Other (OTH) AF: 0.0502 AC: 106 AN: 2110

Alfa AF: 0.0494 Hom.: 185

Bravo AF: 0.0376

Asia WGS AF: 0.102 AC: 354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.13
DANN	Benign	0.33
PhyloP100		-1.2
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: rs16825533; hg19: chr1-17665881;