1-17308646-C-A

Variant names:

• chr1-17308646-C-A
• rs2477132
• NM_012387.3:c.92+332C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012387.3(PADI4):​c.92+332C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.928 in 152,238 control chromosomes in the GnomAD database, including 66,451 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 0.93 (66451 hom., cov: 32)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3	c.92+332C>A		intron_variant	Intron 1 of 15	ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4	c.92+332C>A		intron_variant	Intron 1 of 15	1	NM_012387.3	ENSP00000364597.4
PADI4	ENST00000375453.5	c.92+332C>A		intron_variant	Intron 1 of 3	2		ENSP00000364602.1

Frequencies

GnomAD3 genomes AF: 0.928 AC: 141187 AN: 152120 Hom.: 66424 Cov.: 32

Gnomad AFR AF: 0.754

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.969

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.943

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

GnomAD4 genome AF: 0.928 AC: 141266 AN: 152238 Hom.: 66451 Cov.: 32 AF XY: 0.930 AC XY: 69212 AN XY: 74444

African (AFR) AF: 0.753 AC: 31251 AN: 41486

American (AMR) AF: 0.969 AC: 14813 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 3396 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5173 AN: 5174

South Asian (SAS) AF: 0.999 AC: 4826 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10626 AN: 10626

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67988 AN: 68040

Other (OTH) AF: 0.943 AC: 1994 AN: 2114

Alfa AF: 0.953 Hom.: 8994

Bravo AF: 0.919

Asia WGS AF: 0.983 AC: 3419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.26
DANN	Benign	0.66
PhyloP100		-0.64
PromoterAI		0.026	Neutral
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: rs2477132; hg19: chr1-17635141;