1-17336412-A-T

Position:

• chr1-17336412-A-T

Variant summary

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

The NM_012387.3(PADI4):​c.408+186A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,146 control chromosomes in the GnomAD database, including 32,147 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 0.65 (32147 hom., cov: 33)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PADI4	NM_012387.3	c.408+186A>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.408+186A>T		intron_variant		1	NM_012387.3	ENSP00000364597.4

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98608 AN: 152028 Hom.: 32134 Cov.: 33

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.611

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

GnomAD4 genome AF: 0.648 AC: 98663 AN: 152146 Hom.: 32147 Cov.: 33 AF XY: 0.648 AC XY: 48199 AN XY: 74374

Gnomad4 AFR AF: 0.620

Gnomad4 AMR AF: 0.602

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.603

Alfa AF: 0.662 Hom.: 3974

Bravo AF: 0.638

Asia WGS AF: 0.570 AC: 1983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.7
DANN	Benign	0.58

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: rs1748031; hg19: chr1-17662907; COSMIC: COSV64923490; COSMIC: COSV64923490;