rs2240338

Positions:

• chr1-17347690-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012387.3(PADI4):​c.1048-251C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 151,974 control chromosomes in the GnomAD database, including 10,589 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 0.37 (10589 hom., cov: 31)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PADI4	NM_012387.3	c.1048-251C>T		intron_variant		ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4	c.1048-251C>T		intron_variant		1	NM_012387.3	ENSP00000364597	P1
PADI4	ENST00000468945.1	n.107-251C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55879 AN: 151856 Hom.: 10592 Cov.: 31

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.368 AC: 55904 AN: 151974 Hom.: 10589 Cov.: 31 AF XY: 0.372 AC XY: 27593 AN XY: 74272

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.589

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.358

Alfa AF: 0.360 Hom.: 8012

Bravo AF: 0.376

Asia WGS AF: 0.439 AC: 1522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2240338; hg19: chr1-17674185;