rs34954650

chr1-17363881-T-Cchr1-17363881-T-G

Variant summary

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

The NM_012387.3(PADI4):c.*126T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 634,324 control chromosomes in the GnomAD database, including 94 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 (19 hom., cov: 33)
  • Exomes 𝑓: 0.014 (75 hom.)
• Consequence: PADI4 NM_012387.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.253

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=-0.83).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0122 (1851/152336) while in subpopulation NFE AF= 0.0169 (1148/68028). AF 95% confidence interval is 0.0161. There are 19 homozygotes in gnomad4. There are 899 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PADI4	NM_012387.3	c.*126T>C		3_prime_UTR_variant	16/16	ENST00000375448.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI4	ENST00000375448.4	c.*126T>C		3_prime_UTR_variant	16/16	1	NM_012387.3	P1

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1852 AN: 152218 Hom.: 19 Cov.: 33

Gnomad AFR AF: 0.00326

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.0152

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0169

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.0140 AC: 6735 AN: 481988 Hom.: 75 Cov.: 5 AF XY: 0.0140 AC XY: 3534 AN XY: 253040

Gnomad4 AFR exome AF: 0.00374

Gnomad4 AMR exome AF: 0.0156

Gnomad4 ASJ exome AF: 0.0190

Gnomad4 EAS exome AF: 0.0000645

Gnomad4 SAS exome AF: 0.0120

Gnomad4 FIN exome AF: 0.0162

Gnomad4 NFE exome AF: 0.0152

Gnomad4 OTH exome AF: 0.0148

GnomAD4 genome AF: 0.0122 AC: 1851 AN: 152336 Hom.: 19 Cov.: 33 AF XY: 0.0121 AC XY: 899 AN XY: 74490

Gnomad4 AFR AF: 0.00325

Gnomad4 AMR AF: 0.0150

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0110

Gnomad4 FIN AF: 0.0152

Gnomad4 NFE AF: 0.0169

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.00837 Hom.: 1

Bravo AF: 0.0118

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.3
Dann	Benign	0.81

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: rs34954650; hg19: chr1-17690376;