NM_012387.3:c.1048-214C>T

Variant names:

• chr1-17347727-C-T
• rs2240337
• NM_012387.3:c.1048-214C>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.1048-214C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0944 in 152,252 control chromosomes in the GnomAD database, including 768 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 0.094 (768 hom., cov: 33)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114
• Publications: 18 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.118 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.1048-214C>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.1048-214C>T		intron	N/A	ENSP00000364597.4
	PADI4	ENST00000468945.1	TSL:2	n.107-214C>T		intron	N/A
	PADI4	ENST00000487048.5	TSL:3	n.-200C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0943 AC: 14348 AN: 152134 Hom.: 764 Cov.: 33

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0856

Gnomad EAS AF: 0.0658

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.0773

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0820

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.0944 AC: 14371 AN: 152252 Hom.: 768 Cov.: 33 AF XY: 0.0927 AC XY: 6900 AN XY: 74450

African (AFR) AF: 0.121 AC: 5036 AN: 41556

American (AMR) AF: 0.122 AC: 1867 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0856 AC: 297 AN: 3470

East Asian (EAS) AF: 0.0665 AC: 344 AN: 5174

South Asian (SAS) AF: 0.0245 AC: 118 AN: 4826

European-Finnish (FIN) AF: 0.0773 AC: 820 AN: 10612

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0820 AC: 5579 AN: 68004

Other (OTH) AF: 0.108 AC: 228 AN: 2112

Alfa AF: 0.0858 Hom.: 943

Bravo AF: 0.100

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.89
PhyloP100		-0.11
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: rs2240337; hg19: chr1-17674222;