1-17352218-T-C

Variant names:

• chr1-17352218-T-C
• rs12042956
• NM_012387.3:c.1156-2315T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012387.3(PADI4):​c.1156-2315T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 90,158 control chromosomes in the GnomAD database, including 26 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 0.019 (26 hom., cov: 23)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 3 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.052 is higher than 0.05.

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.1156-2315T>C		intron	N/A	NP_036519.2	Q9UM07

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI4	ENST00000375448.4	TSL:1 MANE Select	c.1156-2315T>C		intron	N/A	ENSP00000364597.4	Q9UM07
	PADI4	ENST00000467001.1	TSL:5	n.57-2315T>C		intron	N/A
	PADI4	ENST00000487048.5	TSL:3	n.123-2315T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0185 AC: 1666 AN: 90102 Hom.: 27 Cov.: 23

Gnomad AFR AF: 0.0548

Gnomad AMI AF: 0.0217

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.00917

Gnomad SAS AF: 0.00671

Gnomad FIN AF: 0.00329

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00974

Gnomad OTH AF: 0.0193

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

GnomAD4 genome AF: 0.0185 AC: 1668 AN: 90158 Hom.: 26 Cov.: 23 AF XY: 0.0195 AC XY: 857 AN XY: 43990

African (AFR) AF: 0.0548 AC: 1027 AN: 18750

American (AMR) AF: 0.00758 AC: 77 AN: 10160

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 24 AN: 2204

East Asian (EAS) AF: 0.00917 AC: 33 AN: 3598

South Asian (SAS) AF: 0.00672 AC: 22 AN: 3272

European-Finnish (FIN) AF: 0.00329 AC: 21 AN: 6386

Middle Eastern (MID) AF: 0.00694 AC: 1 AN: 144

European-Non Finnish (NFE) AF: 0.00974 AC: 427 AN: 43838

Other (OTH) AF: 0.0191 AC: 23 AN: 1206

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.054
DANN	Benign	0.15
PhyloP100		-1.6
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: rs12042956; hg19: chr1-17678713;