rs12731545

Variant names:

• chr1-17348517-G-A
• rs12731545
• NM_012387.3:c.1155+469G>A

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+469G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 152,300 control chromosomes in the GnomAD database, including 34 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 0.016 (34 hom., cov: 33)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774
• 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=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.016 (2434/152300) while in subpopulation NFE AF = 0.0245 (1666/68030). AF 95% confidence interval is 0.0235. There are 34 homozygotes in GnomAd4. There are 1122 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 34 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012387.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI4	NM_012387.3	MANE Select	c.1155+469G>A		intron	N/A	NP_036519.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI4	ENST00000375448.4	TSL:1 MANE Select	c.1155+469G>A		intron	N/A	ENSP00000364597.4
	PADI4	ENST00000487048.5	TSL:3	n.122+469G>A		intron	N/A
	PADI4	ENST00000467001.1	TSL:5	n.-213G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2432 AN: 152182 Hom.: 34 Cov.: 33

Gnomad AFR AF: 0.00437

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00890

Gnomad FIN AF: 0.0151

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.0210

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

GnomAD4 genome AF: 0.0160 AC: 2434 AN: 152300 Hom.: 34 Cov.: 33 AF XY: 0.0151 AC XY: 1122 AN XY: 74474

African (AFR) AF: 0.00438 AC: 182 AN: 41578

American (AMR) AF: 0.0156 AC: 239 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00912 AC: 44 AN: 4826

European-Finnish (FIN) AF: 0.0151 AC: 160 AN: 10614

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0245 AC: 1666 AN: 68030

Other (OTH) AF: 0.0208 AC: 44 AN: 2114

Alfa AF: 0.0197 Hom.: 4

Bravo AF: 0.0157

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.87
DANN	Benign	0.37
PhyloP100		-0.77
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: rs12731545; hg19: chr1-17675012;