1-17348357-T-C

Variant names:

• chr1-17348357-T-C
• rs766449
• NM_012387.3:c.1155+309T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.9).
• 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 rank	MANE	Protein	UniProt
PADI4	NM_012387.3	c.1155+309T>C		intron_variant	Intron 10 of 15	ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4	c.1155+309T>C		intron_variant	Intron 10 of 15	1	NM_012387.3	ENSP00000364597.4
PADI4	ENST00000487048.5	n.122+309T>C		intron_variant	Intron 1 of 3	3
PADI4	ENST00000468945.1	n.*150T>C		downstream_gene_variant		2

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

African (AFR) AF: 0.528 AC: 1586 AN: 3002

American (AMR) AF: 0.494 AC: 1453 AN: 2942

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 1627 AN: 2662

East Asian (EAS) AF: 0.524 AC: 2227 AN: 4252

South Asian (SAS) AF: 0.446 AC: 1725 AN: 3870

European-Finnish (FIN) AF: 0.606 AC: 2358 AN: 3890

Middle Eastern (MID) AF: 0.563 AC: 187 AN: 332

European-Non Finnish (NFE) AF: 0.620 AC: 28391 AN: 45820

Other (OTH) AF: 0.596 AC: 2722 AN: 4564

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

African (AFR) AF: 0.599 AC: 24796 AN: 41414

American (AMR) AF: 0.607 AC: 9263 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2339 AN: 3470

East Asian (EAS) AF: 0.643 AC: 3319 AN: 5160

South Asian (SAS) AF: 0.594 AC: 2865 AN: 4822

European-Finnish (FIN) AF: 0.667 AC: 7039 AN: 10552

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.671 AC: 45644 AN: 67974

Other (OTH) AF: 0.611 AC: 1292 AN: 2114

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
PhyloP100		-0.96
Mutation Taster		=100/0	polymorphism (auto)

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