chr1-17348370-G-A

Variant names:

• chr1-17348370-G-A
• rs12731347
• NM_012387.3:c.1155+322G>A

Variant summary

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

The NM_012387.3(PADI4):​c.1155+322G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0795 in 152,196 control chromosomes in the GnomAD database, including 631 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 0.079 (631 hom., cov: 33)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.22
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3	c.1155+322G>A		intron_variant	Intron 10 of 15	ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4	c.1155+322G>A		intron_variant	Intron 10 of 15	1	NM_012387.3	ENSP00000364597.4
PADI4	ENST00000487048.5	n.122+322G>A		intron_variant	Intron 1 of 3	3
PADI4	ENST00000468945.1	n.*163G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0793 AC: 12063 AN: 152078 Hom.: 627 Cov.: 33

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0544

Gnomad ASJ AF: 0.0469

Gnomad EAS AF: 0.0487

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.0596

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0545

Gnomad OTH AF: 0.0751

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

GnomAD4 genome AF: 0.0795 AC: 12099 AN: 152196 Hom.: 631 Cov.: 33 AF XY: 0.0783 AC XY: 5827 AN XY: 74414

African (AFR) AF: 0.149 AC: 6178 AN: 41510

American (AMR) AF: 0.0542 AC: 829 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0469 AC: 163 AN: 3472

East Asian (EAS) AF: 0.0484 AC: 250 AN: 5164

South Asian (SAS) AF: 0.0290 AC: 140 AN: 4820

European-Finnish (FIN) AF: 0.0596 AC: 633 AN: 10612

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0545 AC: 3708 AN: 68012

Other (OTH) AF: 0.0753 AC: 159 AN: 2112

Alfa AF: 0.0657 Hom.: 101

Bravo AF: 0.0822

Asia WGS AF: 0.0750 AC: 261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.054
DANN	Benign	0.53
PhyloP100		-3.2
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: rs12731347; hg19: chr1-17674865;