rs1635583

Variant names:

• chr1-17338508-G-C
• rs1635583
• NM_012387.3:c.526+353G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-17338508-G-C
• chr1-17338508-G-T

Variant summary

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

The NM_012387.3(PADI4):​c.526+353G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 152,024 control chromosomes in the GnomAD database, including 31,107 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 0.64 (31107 hom., cov: 32)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528
• Publications: 6 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 (NFE) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3	c.526+353G>C		intron_variant	Intron 5 of 15	ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4	c.526+353G>C		intron_variant	Intron 5 of 15	1	NM_012387.3	ENSP00000364597.4

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96880 AN: 151906 Hom.: 31101 Cov.: 32

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.638 AC: 96924 AN: 152024 Hom.: 31107 Cov.: 32 AF XY: 0.638 AC XY: 47372 AN XY: 74290

African (AFR) AF: 0.585 AC: 24267 AN: 41468

American (AMR) AF: 0.598 AC: 9133 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2330 AN: 3470

East Asian (EAS) AF: 0.641 AC: 3306 AN: 5158

South Asian (SAS) AF: 0.585 AC: 2827 AN: 4830

European-Finnish (FIN) AF: 0.684 AC: 7197 AN: 10526

Middle Eastern (MID) AF: 0.627 AC: 183 AN: 292

European-Non Finnish (NFE) AF: 0.674 AC: 45782 AN: 67974

Other (OTH) AF: 0.596 AC: 1259 AN: 2114

Alfa AF: 0.657 Hom.: 4104

Bravo AF: 0.627

Asia WGS AF: 0.566 AC: 1968 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.0
DANN	Benign	0.71
PhyloP100		-0.53
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: rs1635583; hg19: chr1-17665003; COSMIC: COSV64923539; COSMIC: COSV64923539;