Variant chr1-17342013-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_012387.3(PADI4):c.723C>T(p.Pro241=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00265 in 1,613,862 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 55 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 48 hom. )

Consequence

PADI4
NM_012387.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -12.5

Variant links:

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]

PADI4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 1-17342013-C-T is Benign according to our data. Variant chr1-17342013-C-T is described in ClinVar as [Benign]. Clinvar id is 782905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-12.5 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0139 (2116/152258) while in subpopulation AFR AF= 0.0481 (2000/41540). AF 95% confidence interval is 0.0464. There are 55 homozygotes in gnomad4. There are 983 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 55 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PADI4	NM_012387.3 linkuse as main transcript	c.723C>T	p.Pro241=	synonymous_variant	7/16	ENST00000375448.4	NP_036519.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4 linkuse as main transcript	c.723C>T	p.Pro241=	synonymous_variant	7/16	1	NM_012387.3	ENSP00000364597	P1

Frequencies

GnomAD3 genomes

AF:

0.0138

AC:

2105

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0480

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00350

AC:

879

AN:

251364

Hom.:

AF XY:

0.00252

AC XY:

343

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.0483

Gnomad AMR exome

AF:

0.00179

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00148

AC:

2168

AN:

1461604

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

922

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.0518

Gnomad4 AMR exome

AF:

0.00219

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000127

Gnomad4 OTH exome

AF:

0.00286

GnomAD4 genome

AF:

0.0139

AC:

2116

AN:

152258

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

983

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0481

Gnomad4 AMR

AF:

0.00490

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.0119

Alfa

AF:

0.00925

Hom.:

Bravo

AF:

0.0157

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 17, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.017

DANN

Benign

0.60

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over