rs72633848

Variant names:

• chr1-17327880-A-G
• rs72633848
• NM_012387.3:c.93-3089A>G

Variant summary

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

The NM_012387.3(PADI4):​c.93-3089A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 151,528 control chromosomes in the GnomAD database, including 2,081 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 0.14 (2081 hom., cov: 31)
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3	c.93-3089A>G		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.93-3089A>G		intron_variant	Intron 1 of 15	1	NM_012387.3	ENSP00000364597.4
PADI4	ENST00000375453.5	c.93-3089A>G		intron_variant	Intron 1 of 3	2		ENSP00000364602.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21680 AN: 151412 Hom.: 2082 Cov.: 31

Gnomad AFR AF: 0.0426

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.0869

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.143 AC: 21670 AN: 151528 Hom.: 2081 Cov.: 31 AF XY: 0.142 AC XY: 10479 AN XY: 74022

African (AFR) AF: 0.0424 AC: 1751 AN: 41260

American (AMR) AF: 0.111 AC: 1694 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 616 AN: 3460

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5158

South Asian (SAS) AF: 0.0863 AC: 412 AN: 4774

European-Finnish (FIN) AF: 0.227 AC: 2376 AN: 10470

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.208 AC: 14087 AN: 67880

Other (OTH) AF: 0.137 AC: 288 AN: 2098

Alfa AF: 0.170 Hom.: 339

Bravo AF: 0.128

Asia WGS AF: 0.0450 AC: 159 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.54
DANN	Benign	0.55
PhyloP100		-1.0
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: rs72633848; hg19: chr1-17654375; COSMIC: COSV64923371;