1-17338275-A-G

Variant names:

• chr1-17338275-A-G
• rs1635586
• NM_012387.3:c.526+120A>G

Variant summary

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

The ENST00000375448.4(PADI4):​c.526+120A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 678,678 control chromosomes in the GnomAD database, including 143,505 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 (31618 hom., cov: 32)
  • Exomes 𝑓: 0.65 (111887 hom.)
• Consequence: PADI4 ENST00000375448.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643
• Publications: 14 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000375448.4. 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.526+120A>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.526+120A>G		intron	N/A	ENSP00000364597.4

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97782 AN: 151976 Hom.: 31607 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.608

GnomAD4 exome AF: 0.649 AC: 341548 AN: 526584 Hom.: 111887 AF XY: 0.647 AC XY: 184864 AN XY: 285748

African (AFR) AF: 0.601 AC: 8784 AN: 14626

American (AMR) AF: 0.544 AC: 18990 AN: 34916

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 9878 AN: 14902

East Asian (EAS) AF: 0.642 AC: 19692 AN: 30650

South Asian (SAS) AF: 0.575 AC: 33904 AN: 58934

European-Finnish (FIN) AF: 0.676 AC: 26028 AN: 38504

Middle Eastern (MID) AF: 0.595 AC: 1592 AN: 2674

European-Non Finnish (NFE) AF: 0.675 AC: 205451 AN: 304582

Other (OTH) AF: 0.643 AC: 17229 AN: 26796

GnomAD4 genome AF: 0.643 AC: 97834 AN: 152094 Hom.: 31618 Cov.: 32 AF XY: 0.643 AC XY: 47810 AN XY: 74362

African (AFR) AF: 0.604 AC: 25053 AN: 41478

American (AMR) AF: 0.600 AC: 9167 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2329 AN: 3470

East Asian (EAS) AF: 0.641 AC: 3315 AN: 5168

South Asian (SAS) AF: 0.586 AC: 2819 AN: 4814

European-Finnish (FIN) AF: 0.685 AC: 7254 AN: 10590

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45807 AN: 67980

Other (OTH) AF: 0.600 AC: 1269 AN: 2114

Alfa AF: 0.650 Hom.: 15449

Bravo AF: 0.633

Asia WGS AF: 0.569 AC: 1977 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.8
DANN	Benign	0.54
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs1635586; hg19: chr1-17664770; COSMIC: COSV64923530; COSMIC: COSV64923530;