1-17347871-C-T

Variant names:

• chr1-17347871-C-T
• rs6686575
• NM_012387.3:c.1048-70C>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.1048-70C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0481 in 769,762 control chromosomes in the GnomAD database, including 1,103 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 0.060 (366 hom., cov: 33)
  • Exomes 𝑓: 0.045 (737 hom.)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.559
• Publications: 5 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 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.1048-70C>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.1048-70C>T		intron	N/A	ENSP00000364597.4	Q9UM07
	PADI4	ENST00000468945.1	TSL:2	n.107-70C>T		intron	N/A
	PADI4	ENST00000487048.5	TSL:3	n.-56C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0603 AC: 9169 AN: 152122 Hom.: 362 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0386

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.0483

Gnomad SAS AF: 0.0226

Gnomad FIN AF: 0.0562

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0432

Gnomad OTH AF: 0.0578

GnomAD4 exome AF: 0.0451 AC: 27822 AN: 617522 Hom.: 737 AF XY: 0.0442 AC XY: 14226 AN XY: 321596

African (AFR) AF: 0.108 AC: 1728 AN: 16032

American (AMR) AF: 0.0241 AC: 668 AN: 27728

Ashkenazi Jewish (ASJ) AF: 0.0264 AC: 388 AN: 14710

East Asian (EAS) AF: 0.0499 AC: 1587 AN: 31834

South Asian (SAS) AF: 0.0256 AC: 1251 AN: 48832

European-Finnish (FIN) AF: 0.0493 AC: 2273 AN: 46102

Middle Eastern (MID) AF: 0.0300 AC: 114 AN: 3802

European-Non Finnish (NFE) AF: 0.0461 AC: 18323 AN: 397716

Other (OTH) AF: 0.0484 AC: 1490 AN: 30766

GnomAD4 genome AF: 0.0604 AC: 9190 AN: 152240 Hom.: 366 Cov.: 33 AF XY: 0.0603 AC XY: 4488 AN XY: 74442

African (AFR) AF: 0.108 AC: 4472 AN: 41540

American (AMR) AF: 0.0384 AC: 588 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0291 AC: 101 AN: 3470

East Asian (EAS) AF: 0.0482 AC: 249 AN: 5162

South Asian (SAS) AF: 0.0224 AC: 108 AN: 4826

European-Finnish (FIN) AF: 0.0562 AC: 597 AN: 10618

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.0433 AC: 2942 AN: 68010

Other (OTH) AF: 0.0572 AC: 121 AN: 2114

Alfa AF: 0.0670 Hom.: 167

Bravo AF: 0.0604

Asia WGS AF: 0.0660 AC: 227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.9
DANN	Benign	0.82
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6686575;

hg19: chr1-17674366;