Genetic Variant PADI4:c.1047+95C>T (chr1-17346234-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_012387.3(PADI4):c.1047+95C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0383 in 730,382 control chromosomes in the GnomAD database, including 707 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 0.041 ( 132 hom., cov: 32)

Exomes 𝑓: 0.038 ( 575 hom. )

Consequence

PADI4
NM_012387.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.646

Publications

2 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0406 (6175/152210) while in subpopulation NFE AF = 0.0474 (3226/67996). AF 95% confidence interval is 0.0461. There are 132 homozygotes in GnomAd4. There are 2932 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 132 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI4	NM_012387.3 link	c.1047+95C>T		intron_variant	Intron 9 of 15	ENST00000375448.4	NP_036519.2	Q9UM07

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI4	ENST00000375448.4 link	c.1047+95C>T		intron_variant	Intron 9 of 15	1	NM_012387.3	ENSP00000364597.4		Q9UM07
PADI4	ENST00000468945.1 link	n.106+95C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.0406

AC:

6169

AN:

152092

Hom.:

130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0471

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0185

Gnomad ASJ

AF:

0.0236

Gnomad EAS

AF:

0.00136

Gnomad SAS

AF:

0.0253

Gnomad FIN

AF:

0.0365

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0474

Gnomad OTH

AF:

0.0283

GnomAD4 exome

AF:

0.0377

AC:

21790

AN:

578172

Hom.:

575

AF XY:

0.0370

AC XY:

11412

AN XY:

308118

show subpopulations

African (AFR)

AF:

0.0455

AC:

685

AN:

15040

American (AMR)

AF:

0.0130

AC:

338

AN:

25922

Ashkenazi Jewish (ASJ)

AF:

0.0280

AC:

460

AN:

16404

East Asian (EAS)

AF:

0.000579

AC:

AN:

32822

South Asian (SAS)

AF:

0.0201

AC:

1139

AN:

56644

European-Finnish (FIN)

AF:

0.0393

AC:

1868

AN:

47550

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

2340

European-Non Finnish (NFE)

AF:

0.0460

AC:

16142

AN:

351090

Other (OTH)

AF:

0.0365

AC:

1107

AN:

30360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

981

1962

2944

3925

4906

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0406

AC:

6175

AN:

152210

Hom.:

132

Cov.:

AF XY:

0.0394

AC XY:

2932

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0472

AC:

1959

AN:

41540

American (AMR)

AF:

0.0184

AC:

282

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0236

AC:

AN:

3470

East Asian (EAS)

AF:

0.00136

AC:

AN:

5150

South Asian (SAS)

AF:

0.0253

AC:

122

AN:

4822

European-Finnish (FIN)

AF:

0.0365

AC:

388

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0474

AC:

3226

AN:

67996

Other (OTH)

AF:

0.0280

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

304

609

913

1218

1522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0479

Hom.:

Bravo

AF:

0.0395

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.29

(source)

DANN

Benign

0.55

PhyloP100

-0.65

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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1-17346234-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over