rs34170018

Variant names:

• chr1-17363241-C-G
• rs34170018
• NM_012387.3:c.1759-281C>G

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.1759-281C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 152,340 control chromosomes in the GnomAD database, including 19 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)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• Publications: 2 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=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0121 (1843/152340) while in subpopulation NFE AF = 0.0168 (1140/68032). AF 95% confidence interval is 0.0159. There are 19 homozygotes in GnomAd4. There are 893 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012387.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI4	NM_012387.3	MANE Select	c.1759-281C>G		intron	N/A	NP_036519.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI4	ENST00000375448.4	TSL:1 MANE Select	c.1759-281C>G		intron	N/A	ENSP00000364597.4

Frequencies

GnomAD3 genomes AF: 0.0121 AC: 1844 AN: 152222 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: 0.0151

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0168

Gnomad OTH AF: 0.0201

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

GnomAD4 genome AF: 0.0121 AC: 1843 AN: 152340 Hom.: 19 Cov.: 33 AF XY: 0.0120 AC XY: 893 AN XY: 74496

African (AFR) AF: 0.00325 AC: 135 AN: 41584

American (AMR) AF: 0.0150 AC: 230 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.0110 AC: 53 AN: 4830

European-Finnish (FIN) AF: 0.0151 AC: 160 AN: 10618

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0168 AC: 1140 AN: 68032

Other (OTH) AF: 0.0198 AC: 42 AN: 2116

Alfa AF: 0.0134 Hom.: 0

Bravo AF: 0.0118

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.89
PhyloP100		-0.19
Mutation Taster		=98/2	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: rs34170018; hg19: chr1-17689736;