1-17354782-T-C

Variant names:

• chr1-17354782-T-C
• rs6683201
• NM_012387.3:c.1310+95T>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.1310+95T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 1,212,040 control chromosomes in the GnomAD database, including 310,008 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 0.75 (43774 hom., cov: 32)
  • Exomes 𝑓: 0.71 (266234 hom.)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 22 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 = 0.886 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.1310+95T>C		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.1310+95T>C		intron	N/A	ENSP00000364597.4
	PADI4	ENST00000467001.1	TSL:5	n.211+95T>C		intron	N/A
	PADI4	ENST00000487048.5	TSL:3	n.277+95T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114201 AN: 151990 Hom.: 43725 Cov.: 32

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.793

GnomAD4 exome AF: 0.707 AC: 749138 AN: 1059932 Hom.: 266234 AF XY: 0.707 AC XY: 371798 AN XY: 525786

African (AFR) AF: 0.909 AC: 22689 AN: 24956

American (AMR) AF: 0.679 AC: 14282 AN: 21040

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 14488 AN: 17500

East Asian (EAS) AF: 0.792 AC: 28219 AN: 35630

South Asian (SAS) AF: 0.719 AC: 43070 AN: 59940

European-Finnish (FIN) AF: 0.623 AC: 23493 AN: 37698

Middle Eastern (MID) AF: 0.859 AC: 2965 AN: 3452

European-Non Finnish (NFE) AF: 0.696 AC: 566488 AN: 813588

Other (OTH) AF: 0.725 AC: 33444 AN: 46128

GnomAD4 genome AF: 0.751 AC: 114303 AN: 152108 Hom.: 43774 Cov.: 32 AF XY: 0.743 AC XY: 55260 AN XY: 74370

African (AFR) AF: 0.894 AC: 37084 AN: 41504

American (AMR) AF: 0.695 AC: 10625 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 2862 AN: 3470

East Asian (EAS) AF: 0.773 AC: 4002 AN: 5178

South Asian (SAS) AF: 0.706 AC: 3401 AN: 4814

European-Finnish (FIN) AF: 0.607 AC: 6409 AN: 10566

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47300 AN: 67978

Other (OTH) AF: 0.792 AC: 1674 AN: 2114

Alfa AF: 0.724 Hom.: 68449

Bravo AF: 0.766

Asia WGS AF: 0.736 AC: 2558 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	1.6
DANN	Benign	0.31
PhyloP100		-1.1
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: rs6683201; hg19: chr1-17681277; COSMIC: COSV64923587;