1-17354312-C-T

Variant names:

• chr1-17354312-C-T
• rs3094881
• NM_012387.3:c.1156-221C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.96).
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 98 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3	c.1156-221C>T		intron_variant	Intron 10 of 15	ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4	c.1156-221C>T		intron_variant	Intron 10 of 15	1	NM_012387.3	ENSP00000364597.4
PADI4	ENST00000467001.1	n.57-221C>T		intron_variant	Intron 1 of 4	5
PADI4	ENST00000487048.5	n.123-221C>T		intron_variant	Intron 1 of 3	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

African (AFR) AF: 0.0196 AC: 813 AN: 41542

American (AMR) AF: 0.0170 AC: 260 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 69 AN: 3472

East Asian (EAS) AF: 0.0324 AC: 168 AN: 5178

South Asian (SAS) AF: 0.0110 AC: 53 AN: 4814

European-Finnish (FIN) AF: 0.0497 AC: 525 AN: 10574

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0404 AC: 2746 AN: 68014

Other (OTH) AF: 0.0232 AC: 49 AN: 2112

Alfa AF: 0.0368 Hom.: 163

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
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

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