1-17357031-T-G

Variant names:

• chr1-17357031-T-G
• rs1635564
• NM_012387.3:c.1558+572T>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.1558+572T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 152,072 control chromosomes in the GnomAD database, including 45,345 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 0.76 (45345 hom., cov: 31)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 16 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI4	NM_012387.3	MANE Select	c.1558+572T>G		intron	N/A	NP_036519.2	Q9UM07

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI4	ENST00000375448.4	TSL:1 MANE Select	c.1558+572T>G		intron	N/A	ENSP00000364597.4	Q9UM07
	PADI4	ENST00000467001.1	TSL:5	n.459+572T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115944 AN: 151954 Hom.: 45289 Cov.: 31

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.767

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

GnomAD4 genome AF: 0.763 AC: 116053 AN: 152072 Hom.: 45345 Cov.: 31 AF XY: 0.755 AC XY: 56128 AN XY: 74300

African (AFR) AF: 0.936 AC: 38868 AN: 41526

American (AMR) AF: 0.679 AC: 10365 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.834 AC: 2893 AN: 3468

East Asian (EAS) AF: 0.792 AC: 4081 AN: 5152

South Asian (SAS) AF: 0.655 AC: 3152 AN: 4810

European-Finnish (FIN) AF: 0.635 AC: 6711 AN: 10566

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47437 AN: 67974

Other (OTH) AF: 0.764 AC: 1617 AN: 2116

Alfa AF: 0.724 Hom.: 145975

Bravo AF: 0.778

Asia WGS AF: 0.732 AC: 2546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.44
PhyloP100		-1.5
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: rs1635564; hg19: chr1-17683526; COSMIC: COSV64923618; COSMIC: COSV64923618;