rs1635570

Variant names:

• chr1-17348106-C-T
• rs1635570
• NM_012387.3:c.1155+58C>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.1155+58C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 1,122,334 control chromosomes in the GnomAD database, including 1,039 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 0.028 (94 hom., cov: 33)
  • Exomes 𝑓: 0.037 (945 hom.)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326
• Publications: 4 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 = 0.0285 (4336/152330) while in subpopulation NFE AF = 0.0472 (3214/68038). AF 95% confidence interval is 0.0459. There are 94 homozygotes in GnomAd4. There are 2034 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 94 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.1155+58C>T		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.1155+58C>T		intron	N/A	ENSP00000364597.4	Q9UM07
	PADI4	ENST00000468945.1	TSL:2	n.272C>T		non_coding_transcript_exon	Exon 2 of 2
	PADI4	ENST00000487048.5	TSL:3	n.122+58C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0285 AC: 4335 AN: 152212 Hom.: 94 Cov.: 33

Gnomad AFR AF: 0.00743

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0150

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.0367

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0472

Gnomad OTH AF: 0.0182

GnomAD2 exomes AF: 0.0288 AC: 6592 AN: 228496 AF XY: 0.0290

Gnomad AFR exome AF: 0.00743

Gnomad AMR exome AF: 0.00933

Gnomad ASJ exome AF: 0.0306

Gnomad EAS exome AF: 0.000300

Gnomad FIN exome AF: 0.0386

Gnomad NFE exome AF: 0.0470

Gnomad OTH exome AF: 0.0227

GnomAD4 exome AF: 0.0373 AC: 36144 AN: 970004 Hom.: 945 Cov.: 13 AF XY: 0.0365 AC XY: 18296 AN XY: 501608

African (AFR) AF: 0.00743 AC: 177 AN: 23808

American (AMR) AF: 0.00953 AC: 405 AN: 42510

Ashkenazi Jewish (ASJ) AF: 0.0291 AC: 653 AN: 22452

East Asian (EAS) AF: 0.000136 AC: 5 AN: 36640

South Asian (SAS) AF: 0.00711 AC: 530 AN: 74592

European-Finnish (FIN) AF: 0.0394 AC: 2022 AN: 51324

Middle Eastern (MID) AF: 0.00748 AC: 36 AN: 4810

European-Non Finnish (NFE) AF: 0.0461 AC: 30857 AN: 669724

Other (OTH) AF: 0.0331 AC: 1459 AN: 44144

GnomAD4 genome AF: 0.0285 AC: 4336 AN: 152330 Hom.: 94 Cov.: 33 AF XY: 0.0273 AC XY: 2034 AN XY: 74486

African (AFR) AF: 0.00741 AC: 308 AN: 41574

American (AMR) AF: 0.0150 AC: 230 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 80 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.00518 AC: 25 AN: 4828

European-Finnish (FIN) AF: 0.0367 AC: 390 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0472 AC: 3214 AN: 68038

Other (OTH) AF: 0.0180 AC: 38 AN: 2112

Alfa AF: 0.0278 Hom.: 24

Bravo AF: 0.0257

Asia WGS AF: 0.00577 AC: 21 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	1.8
DANN	Benign	0.66
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

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: rs1635570; hg19: chr1-17674601; COSMIC: COSV64924580; COSMIC: COSV64924580;