NM_012387.3:c.1559-159T>C

Variant names:

• chr1-17358679-T-C
• rs2428735
• NM_012387.3:c.1559-159T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012387.3(PADI4):​c.1559-159T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 151,592 control chromosomes in the GnomAD database, including 42,654 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 0.74 (42654 hom., cov: 31)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3	c.1559-159T>C		intron_variant	Intron 13 of 15	ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4	c.1559-159T>C		intron_variant	Intron 13 of 15	1	NM_012387.3	ENSP00000364597.4
PADI4	ENST00000467001.1	n.460-159T>C		intron_variant	Intron 4 of 4	5

Frequencies

GnomAD3 genomes AF: 0.744 AC: 112696 AN: 151476 Hom.: 42609 Cov.: 31

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.744 AC: 112792 AN: 151592 Hom.: 42654 Cov.: 31 AF XY: 0.736 AC XY: 54564 AN XY: 74098

African (AFR) AF: 0.870 AC: 35924 AN: 41310

American (AMR) AF: 0.673 AC: 10224 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.834 AC: 2889 AN: 3466

East Asian (EAS) AF: 0.793 AC: 4098 AN: 5170

South Asian (SAS) AF: 0.654 AC: 3143 AN: 4806

European-Finnish (FIN) AF: 0.636 AC: 6696 AN: 10522

Middle Eastern (MID) AF: 0.793 AC: 230 AN: 290

European-Non Finnish (NFE) AF: 0.698 AC: 47310 AN: 67812

Other (OTH) AF: 0.755 AC: 1589 AN: 2106

Alfa AF: 0.710 Hom.: 19237

Bravo AF: 0.755

Asia WGS AF: 0.725 AC: 2520 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.2
DANN	Benign	0.53
PhyloP100		-0.17
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: rs2428735; hg19: chr1-17685174; COSMIC: COSV64923633; COSMIC: COSV64923633;