1-17359518-C-T

Variant names:

• chr1-17359518-C-T
• rs6673924
• NM_012387.3:c.1758+110C>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+110C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00348 in 1,445,642 control chromosomes in the GnomAD database, including 142 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 0.017 (76 hom., cov: 31)
  • Exomes 𝑓: 0.0019 (66 hom.)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.419
• Publications: 1 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0569 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.1758+110C>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.1758+110C>T		intron	N/A	ENSP00000364597.4	Q9UM07

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 2608 AN: 152136 Hom.: 76 Cov.: 31

Gnomad AFR AF: 0.0587

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00760

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.00187 AC: 2415 AN: 1293388 Hom.: 66 AF XY: 0.00169 AC XY: 1086 AN XY: 644312

African (AFR) AF: 0.0600 AC: 1774 AN: 29560

American (AMR) AF: 0.00535 AC: 199 AN: 37222

Ashkenazi Jewish (ASJ) AF: 0.000468 AC: 10 AN: 21378

East Asian (EAS) AF: 0.00 AC: 0 AN: 38150

South Asian (SAS) AF: 0.000134 AC: 10 AN: 74832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48702

Middle Eastern (MID) AF: 0.00314 AC: 14 AN: 4458

European-Non Finnish (NFE) AF: 0.000170 AC: 167 AN: 985080

Other (OTH) AF: 0.00446 AC: 241 AN: 54006

GnomAD4 genome AF: 0.0172 AC: 2623 AN: 152254 Hom.: 76 Cov.: 31 AF XY: 0.0173 AC XY: 1285 AN XY: 74430

African (AFR) AF: 0.0589 AC: 2446 AN: 41544

American (AMR) AF: 0.00759 AC: 116 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68024

Other (OTH) AF: 0.0151 AC: 32 AN: 2116

Alfa AF: 0.00276 Hom.: 1

Bravo AF: 0.0191

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.50
DANN	Benign	0.37
PhyloP100		0.42
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: rs6673924; hg19: chr1-17686013;