rs2240338

Variant names:

• chr1-17347690-C-T
• rs2240338
• NM_012387.3:c.1048-251C>T

Variant summary

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

The NM_012387.3(PADI4):​c.1048-251C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 151,974 control chromosomes in the GnomAD database, including 10,589 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 0.37 (10589 hom., cov: 31)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712
• Publications: 7 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 (EAS) allele frequency at 95% confidence interval = 0.572 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.1048-251C>T		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.1048-251C>T		intron	N/A	ENSP00000364597.4
	PADI4	ENST00000468945.1	TSL:2	n.107-251C>T		intron	N/A
	PADI4	ENST00000487048.5	TSL:3	n.-237C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55879 AN: 151856 Hom.: 10592 Cov.: 31

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.368 AC: 55904 AN: 151974 Hom.: 10589 Cov.: 31 AF XY: 0.372 AC XY: 27593 AN XY: 74272

African (AFR) AF: 0.354 AC: 14680 AN: 41448

American (AMR) AF: 0.417 AC: 6362 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1467 AN: 3470

East Asian (EAS) AF: 0.589 AC: 3028 AN: 5138

South Asian (SAS) AF: 0.449 AC: 2159 AN: 4808

European-Finnish (FIN) AF: 0.333 AC: 3520 AN: 10582

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.348 AC: 23626 AN: 67950

Other (OTH) AF: 0.358 AC: 756 AN: 2112

Alfa AF: 0.361 Hom.: 10691

Bravo AF: 0.376

Asia WGS AF: 0.439 AC: 1522 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	2.0
DANN	Benign	0.33
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2240338; hg19: chr1-17674185;