1-17334202-T-C

Variant names:

• chr1-17334202-T-C
• rs1548323
• NM_012387.3:c.340+193T>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.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
• 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=-0.9).
• 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 rank	MANE	Protein	UniProt
PADI4	NM_012387.3	c.340+193T>C		intron_variant	Intron 3 of 15	ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4	c.340+193T>C		intron_variant	Intron 3 of 15	1	NM_012387.3	ENSP00000364597.4
PADI4	ENST00000375453.5	c.341-122T>C		intron_variant	Intron 3 of 3	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

African (AFR) AF: 0.479 AC: 5734 AN: 11978

American (AMR) AF: 0.528 AC: 9657 AN: 18284

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 7847 AN: 13040

East Asian (EAS) AF: 0.591 AC: 17318 AN: 29314

South Asian (SAS) AF: 0.523 AC: 22711 AN: 43384

European-Finnish (FIN) AF: 0.587 AC: 24648 AN: 41970

Middle Eastern (MID) AF: 0.545 AC: 1253 AN: 2298

European-Non Finnish (NFE) AF: 0.578 AC: 145993 AN: 252690

Other (OTH) AF: 0.557 AC: 13725 AN: 24640

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

African (AFR) AF: 0.483 AC: 20041 AN: 41454

American (AMR) AF: 0.549 AC: 8388 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2145 AN: 3472

East Asian (EAS) AF: 0.592 AC: 3064 AN: 5180

South Asian (SAS) AF: 0.537 AC: 2589 AN: 4820

European-Finnish (FIN) AF: 0.593 AC: 6259 AN: 10560

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.584 AC: 39695 AN: 67980

Other (OTH) AF: 0.526 AC: 1109 AN: 2108

Alfa AF: 0.548 Hom.: 3304

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
PhyloP100		-1.5
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: rs1548323; hg19: chr1-17660697; COSMIC: COSV64923458;