NM_012387.3:c.1047+96G>A

Variant names:

• chr1-17346235-G-A
• rs2301888
• NM_012387.3:c.1047+96G>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.1047+96G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 704,740 control chromosomes in the GnomAD database, including 47,023 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 0.32 (8441 hom., cov: 31)
  • Exomes 𝑓: 0.36 (38582 hom.)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 41 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 = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3	c.1047+96G>A		intron_variant	Intron 9 of 15	ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4	c.1047+96G>A		intron_variant	Intron 9 of 15	1	NM_012387.3	ENSP00000364597.4
PADI4	ENST00000468945.1	n.106+96G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48116 AN: 151850 Hom.: 8451 Cov.: 31

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.329

GnomAD4 exome AF: 0.364 AC: 201481 AN: 552772 Hom.: 38582 AF XY: 0.368 AC XY: 108548 AN XY: 294726

African (AFR) AF: 0.174 AC: 2539 AN: 14624

American (AMR) AF: 0.396 AC: 9500 AN: 24008

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 6377 AN: 15756

East Asian (EAS) AF: 0.578 AC: 18561 AN: 32096

South Asian (SAS) AF: 0.429 AC: 23372 AN: 54502

European-Finnish (FIN) AF: 0.327 AC: 15173 AN: 46426

Middle Eastern (MID) AF: 0.375 AC: 835 AN: 2228

European-Non Finnish (NFE) AF: 0.343 AC: 114604 AN: 333828

Other (OTH) AF: 0.359 AC: 10520 AN: 29304

GnomAD4 genome AF: 0.316 AC: 48096 AN: 151968 Hom.: 8441 Cov.: 31 AF XY: 0.323 AC XY: 23970 AN XY: 74298

African (AFR) AF: 0.178 AC: 7371 AN: 41476

American (AMR) AF: 0.395 AC: 6040 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1452 AN: 3468

East Asian (EAS) AF: 0.584 AC: 2990 AN: 5116

South Asian (SAS) AF: 0.450 AC: 2170 AN: 4822

European-Finnish (FIN) AF: 0.333 AC: 3523 AN: 10572

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.347 AC: 23558 AN: 67926

Other (OTH) AF: 0.324 AC: 684 AN: 2112

Alfa AF: 0.356 Hom.: 9128

Bravo AF: 0.318

Asia WGS AF: 0.421 AC: 1462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.5
DANN	Benign	0.47
PhyloP100		1.4
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: rs2301888; hg19: chr1-17672730;