1-17356662-A-G

Variant names:

• chr1-17356662-A-G
• rs1635566
• NM_012387.3:c.1558+203A>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+203A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 152,040 control chromosomes in the GnomAD database, including 37,697 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 0.70 (37697 hom., cov: 31)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309
• Publications: 8 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.767 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI4	NM_012387.3	MANE Select	c.1558+203A>G		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.1558+203A>G		intron	N/A	ENSP00000364597.4
	PADI4	ENST00000467001.1	TSL:5	n.459+203A>G		intron	N/A
	PADI4	ENST00000487048.5	TSL:3	n.*215A>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106683 AN: 151922 Hom.: 37672 Cov.: 31

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.833

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.702 AC: 106752 AN: 152040 Hom.: 37697 Cov.: 31 AF XY: 0.696 AC XY: 51684 AN XY: 74280

African (AFR) AF: 0.728 AC: 30181 AN: 41472

American (AMR) AF: 0.651 AC: 9956 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.833 AC: 2890 AN: 3470

East Asian (EAS) AF: 0.787 AC: 4053 AN: 5148

South Asian (SAS) AF: 0.656 AC: 3162 AN: 4820

European-Finnish (FIN) AF: 0.635 AC: 6703 AN: 10560

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47367 AN: 67964

Other (OTH) AF: 0.721 AC: 1523 AN: 2112

Alfa AF: 0.705 Hom.: 5223

Bravo AF: 0.708

Asia WGS AF: 0.717 AC: 2492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.85
PhyloP100		0.31
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: rs1635566; hg19: chr1-17683157; COSMIC: COSV64923604; COSMIC: COSV64923604;