rs12754450

Variant names:

• chr1-17348561-A-C
• rs12754450
• NM_012387.3:c.1155+513A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_012387.3(PADI4):​c.1155+513A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0211 in 152,280 control chromosomes in the GnomAD database, including 41 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 0.021 (41 hom., cov: 33)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521
• Publications: 1 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=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0211 (3211/152280) while in subpopulation NFE AF = 0.0245 (1668/68010). AF 95% confidence interval is 0.0235. There are 41 homozygotes in GnomAd4. There are 1487 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3	c.1155+513A>C		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+513A>C		intron_variant	Intron 10 of 15	1	NM_012387.3	ENSP00000364597.4
PADI4	ENST00000487048.5	n.122+513A>C		intron_variant	Intron 1 of 3	3
PADI4	ENST00000467001.1	n.-169A>C		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 3207 AN: 152162 Hom.: 41 Cov.: 33

Gnomad AFR AF: 0.0219

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00890

Gnomad FIN AF: 0.0151

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.0235

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

GnomAD4 genome AF: 0.0211 AC: 3211 AN: 152280 Hom.: 41 Cov.: 33 AF XY: 0.0200 AC XY: 1487 AN XY: 74460

African (AFR) AF: 0.0219 AC: 911 AN: 41564

American (AMR) AF: 0.0179 AC: 274 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00911 AC: 44 AN: 4830

European-Finnish (FIN) AF: 0.0151 AC: 160 AN: 10618

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0245 AC: 1668 AN: 68010

Other (OTH) AF: 0.0242 AC: 51 AN: 2110

Alfa AF: 0.0232 Hom.: 14

Bravo AF: 0.0215

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.67
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism

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: rs12754450; hg19: chr1-17675056;