1-17346234-C-T

Position:

• chr1-17346234-C-T

Variant summary

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

The NM_012387.3(PADI4):​c.1047+95C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0383 in 730,382 control chromosomes in the GnomAD database, including 707 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 0.041 (132 hom., cov: 32)
  • Exomes 𝑓: 0.038 (575 hom.)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646

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]

PADI4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0406 (6175/152210) while in subpopulation NFE AF= 0.0474 (3226/67996). AF 95% confidence interval is 0.0461. There are 132 homozygotes in gnomad4. There are 2932 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 132 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PADI4	NM_012387.3	c.1047+95C>T		intron_variant		ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4	c.1047+95C>T		intron_variant		1	NM_012387.3	ENSP00000364597.4
PADI4	ENST00000468945.1	n.106+95C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0406 AC: 6169 AN: 152092 Hom.: 130 Cov.: 32

Gnomad AFR AF: 0.0471

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0185

Gnomad ASJ AF: 0.0236

Gnomad EAS AF: 0.00136

Gnomad SAS AF: 0.0253

Gnomad FIN AF: 0.0365

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0474

Gnomad OTH AF: 0.0283

GnomAD4 exome AF: 0.0377 AC: 21790 AN: 578172 Hom.: 575 AF XY: 0.0370 AC XY: 11412 AN XY: 308118

Gnomad4 AFR exome AF: 0.0455

Gnomad4 AMR exome AF: 0.0130

Gnomad4 ASJ exome AF: 0.0280

Gnomad4 EAS exome AF: 0.000579

Gnomad4 SAS exome AF: 0.0201

Gnomad4 FIN exome AF: 0.0393

Gnomad4 NFE exome AF: 0.0460

Gnomad4 OTH exome AF: 0.0365

GnomAD4 genome AF: 0.0406 AC: 6175 AN: 152210 Hom.: 132 Cov.: 32 AF XY: 0.0394 AC XY: 2932 AN XY: 74426

Gnomad4 AFR AF: 0.0472

Gnomad4 AMR AF: 0.0184

Gnomad4 ASJ AF: 0.0236

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.0253

Gnomad4 FIN AF: 0.0365

Gnomad4 NFE AF: 0.0474

Gnomad4 OTH AF: 0.0280

Alfa AF: 0.0482 Hom.: 25

Bravo AF: 0.0395

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.29
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1635571; hg19: chr1-17672729;