1-17360532-C-T

Variant names:

• chr1-17360532-C-T
• rs1635561
• NM_012387.3:c.1758+1124C>T

Variant summary

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

The NM_012387.3(PADI4):​c.1758+1124C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,010 control chromosomes in the GnomAD database, including 4,470 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 0.24 (4470 hom., cov: 31)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402
• Publications: 7 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=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3	c.1758+1124C>T		intron_variant	Intron 15 of 15	ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4	c.1758+1124C>T		intron_variant	Intron 15 of 15	1	NM_012387.3	ENSP00000364597.4

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36290 AN: 151890 Hom.: 4475 Cov.: 31

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.239 AC: 36310 AN: 152010 Hom.: 4470 Cov.: 31 AF XY: 0.234 AC XY: 17395 AN XY: 74290

African (AFR) AF: 0.233 AC: 9642 AN: 41456

American (AMR) AF: 0.190 AC: 2895 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1158 AN: 3466

East Asian (EAS) AF: 0.306 AC: 1577 AN: 5152

South Asian (SAS) AF: 0.240 AC: 1155 AN: 4818

European-Finnish (FIN) AF: 0.179 AC: 1897 AN: 10570

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17123 AN: 67954

Other (OTH) AF: 0.251 AC: 530 AN: 2114

Alfa AF: 0.253 Hom.: 19518

Bravo AF: 0.242

Asia WGS AF: 0.243 AC: 847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.5
DANN	Benign	0.77
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1635561; hg19: chr1-17687027;