rs12089685

Positions:

• chr1-17337985-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_012387.3(PADI4):​c.409-53T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 997,606 control chromosomes in the GnomAD database, including 60 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 0.012 (35 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (25 hom.)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.82

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0122 (1854/152074) while in subpopulation AFR AF= 0.0414 (1720/41500). AF 95% confidence interval is 0.0398. There are 35 homozygotes in gnomad4. There are 877 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PADI4	NM_012387.3	c.409-53T>C		intron_variant		ENST00000375448.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI4	ENST00000375448.4	c.409-53T>C		intron_variant		1	NM_012387.3	P1

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1854 AN: 151956 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.0416

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00584

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.00149 AC: 1257 AN: 845532 Hom.: 25 AF XY: 0.00128 AC XY: 570 AN XY: 443994

Gnomad4 AFR exome AF: 0.0389

Gnomad4 AMR exome AF: 0.00341

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000992

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000230

Gnomad4 OTH exome AF: 0.00360

GnomAD4 genome AF: 0.0122 AC: 1854 AN: 152074 Hom.: 35 Cov.: 32 AF XY: 0.0118 AC XY: 877 AN XY: 74366

Gnomad4 AFR AF: 0.0414

Gnomad4 AMR AF: 0.00584

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0119

Alfa AF: 0.00860 Hom.: 1

Bravo AF: 0.0135

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.040
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs12089685; hg19: chr1-17664480;