rs1748011

Positions:

• chr1-17356786-C-A
• chr1-17356786-C-G
• chr1-17356786-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.1558+327C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 149,242 control chromosomes in the GnomAD database, including 40,084 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 0.73 (40084 hom., cov: 28)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PADI4	NM_012387.3	c.1558+327C>A		intron_variant		ENST00000375448.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI4	ENST00000375448.4	c.1558+327C>A		intron_variant		1	NM_012387.3	P1
PADI4	ENST00000467001.1	n.459+327C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.734 AC: 109499 AN: 149142 Hom.: 40042 Cov.: 28

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.780

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.750

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

GnomAD4 genome AF: 0.734 AC: 109594 AN: 149242 Hom.: 40084 Cov.: 28 AF XY: 0.732 AC XY: 53064 AN XY: 72522

Gnomad4 AFR AF: 0.810

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.834

Gnomad4 EAS AF: 0.795

Gnomad4 SAS AF: 0.668

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.748

Alfa AF: 0.671 Hom.: 4663

Bravo AF: 0.732

Asia WGS AF: 0.723 AC: 2513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.049
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs1748011; hg19: chr1-17683281; COSMIC: COSV64923607; COSMIC: COSV64923607;