1-17334202-T-C

Position:

• chr1-17334202-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012387.3(PADI4):​c.340+193T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 589,654 control chromosomes in the GnomAD database, including 94,756 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 0.55 (23477 hom., cov: 32)
  • Exomes 𝑓: 0.57 (71279 hom.)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PADI4	NM_012387.3	c.340+193T>C		intron_variant		ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4	c.340+193T>C		intron_variant		1	NM_012387.3	ENSP00000364597.4
PADI4	ENST00000375453.5	c.341-122T>C		intron_variant		2		ENSP00000364602.1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84021 AN: 151936 Hom.: 23485 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.533

GnomAD4 exome AF: 0.569 AC: 248886 AN: 437598 Hom.: 71279 AF XY: 0.567 AC XY: 130226 AN XY: 229620

Gnomad4 AFR exome AF: 0.479

Gnomad4 AMR exome AF: 0.528

Gnomad4 ASJ exome AF: 0.602

Gnomad4 EAS exome AF: 0.591

Gnomad4 SAS exome AF: 0.523

Gnomad4 FIN exome AF: 0.587

Gnomad4 NFE exome AF: 0.578

Gnomad4 OTH exome AF: 0.557

GnomAD4 genome AF: 0.553 AC: 84047 AN: 152056 Hom.: 23477 Cov.: 32 AF XY: 0.554 AC XY: 41141 AN XY: 74326

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.537

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.526

Alfa AF: 0.550 Hom.: 3206

Bravo AF: 0.546

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs1548323; hg19: chr1-17660697; COSMIC: COSV64923458;