rs766449

Positions:

• chr1-17348357-T-C

Variant summary

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

The NM_012387.3(PADI4):​c.1155+309T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 223,308 control chromosomes in the GnomAD database, including 44,632 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 0.64 (31353 hom., cov: 33)
  • Exomes 𝑓: 0.59 (13279 hom.)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.962

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PADI4	NM_012387.3	c.1155+309T>C		intron_variant		ENST00000375448.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PADI4	ENST00000375448.4	c.1155+309T>C		intron_variant		1	NM_012387.3	P1
PADI4	ENST00000487048.5	n.122+309T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97345 AN: 151856 Hom.: 31342 Cov.: 33

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.618

GnomAD4 exome AF: 0.593 AC: 42276 AN: 71334 Hom.: 13279 AF XY: 0.590 AC XY: 21769 AN XY: 36890

Gnomad4 AFR exome AF: 0.528

Gnomad4 AMR exome AF: 0.494

Gnomad4 ASJ exome AF: 0.611

Gnomad4 EAS exome AF: 0.524

Gnomad4 SAS exome AF: 0.446

Gnomad4 FIN exome AF: 0.606

Gnomad4 NFE exome AF: 0.620

Gnomad4 OTH exome AF: 0.596

GnomAD4 genome AF: 0.641 AC: 97404 AN: 151974 Hom.: 31353 Cov.: 33 AF XY: 0.640 AC XY: 47536 AN XY: 74258

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.643

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.667

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.611

Alfa AF: 0.663 Hom.: 6817

Bravo AF: 0.634

Asia WGS AF: 0.582 AC: 2022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.24
DANN	Benign	0.31

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: rs766449; hg19: chr1-17674852; COSMIC: COSV64923572; COSMIC: COSV64923572;