rs3094881

Positions:

• chr1-17354312-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.1156-221C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0309 in 152,192 control chromosomes in the GnomAD database, including 98 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 0.031 (98 hom., cov: 32)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-0.96).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0309 (4700/152192) while in subpopulation NFE AF= 0.0404 (2746/68014). AF 95% confidence interval is 0.0391. There are 98 homozygotes in gnomad4. There are 2318 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 98 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PADI4	NM_012387.3	c.1156-221C>T		intron_variant		ENST00000375448.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI4	ENST00000375448.4	c.1156-221C>T		intron_variant		1	NM_012387.3	P1
PADI4	ENST00000467001.1	n.57-221C>T		intron_variant, non_coding_transcript_variant		5
PADI4	ENST00000487048.5	n.123-221C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0308 AC: 4687 AN: 152074 Hom.: 97 Cov.: 32

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0170

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.0326

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.0497

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0404

Gnomad OTH AF: 0.0239

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

GnomAD4 genome AF: 0.0309 AC: 4700 AN: 152192 Hom.: 98 Cov.: 32 AF XY: 0.0312 AC XY: 2318 AN XY: 74390

Gnomad4 AFR AF: 0.0196

Gnomad4 AMR AF: 0.0170

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.0324

Gnomad4 SAS AF: 0.0110

Gnomad4 FIN AF: 0.0497

Gnomad4 NFE AF: 0.0404

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0364 Hom.: 17

Bravo AF: 0.0274

Asia WGS AF: 0.0200 AC: 74 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0010
DANN	Benign	0.62

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: rs3094881; hg19: chr1-17680807; COSMIC: COSV105827697;