rs12746451

Variant names:

• chr1-17348326-C-T
• rs12746451
• NM_012387.3:c.1155+278C>T

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.87).
• 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 rank	MANE	Protein	UniProt
PADI4	NM_012387.3	c.1155+278C>T		intron_variant	Intron 10 of 15	ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4	c.1155+278C>T		intron_variant	Intron 10 of 15	1	NM_012387.3	ENSP00000364597.4
PADI4	ENST00000487048.5	n.122+278C>T		intron_variant	Intron 1 of 3	3
PADI4	ENST00000468945.1	n.*119C>T		downstream_gene_variant		2

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

African (AFR) AF: 0.185 AC: 912 AN: 4942

American (AMR) AF: 0.0514 AC: 270 AN: 5254

Ashkenazi Jewish (ASJ) AF: 0.0539 AC: 257 AN: 4766

East Asian (EAS) AF: 0.0599 AC: 521 AN: 8698

South Asian (SAS) AF: 0.0458 AC: 343 AN: 7496

European-Finnish (FIN) AF: 0.0748 AC: 580 AN: 7754

Middle Eastern (MID) AF: 0.0817 AC: 50 AN: 612

European-Non Finnish (NFE) AF: 0.0769 AC: 6392 AN: 83172

Other (OTH) AF: 0.0822 AC: 685 AN: 8338

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

African (AFR) AF: 0.162 AC: 6721 AN: 41522

American (AMR) AF: 0.0592 AC: 906 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0487 AC: 169 AN: 3468

East Asian (EAS) AF: 0.0485 AC: 251 AN: 5176

South Asian (SAS) AF: 0.0319 AC: 154 AN: 4834

European-Finnish (FIN) AF: 0.0714 AC: 758 AN: 10612

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0680 AC: 4622 AN: 68012

Other (OTH) AF: 0.0876 AC: 185 AN: 2112

Alfa AF: 0.0732 Hom.: 652

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
PhyloP100		-0.99
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12746451; hg19: chr1-17674821;