dbSNP rs2977310: PADI1:c.1459-121T>C (chr1-17238495-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013358.3(PADI1):c.1459-121T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 438,168 control chromosomes in the GnomAD database, including 54,210 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 0.51 ( 20463 hom., cov: 32)

Exomes 𝑓: 0.48 ( 33747 hom. )

Consequence

PADI1
NM_013358.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.31

Publications

8 publications found

Variant links:

Genes affected

PADI1 (HGNC:18367): (peptidyl arginine deiminase 1) This gene encodes a member of the peptidyl arginine deiminase family of enzymes, which catalyze the post-translational deimination of proteins by converting arginine residues into citrullines in the presence of calcium ions. The family members have distinct substrate specificities and tissue-specific expression patterns. The type I enzyme is involved in the late stages of epidermal differentiation, where it deiminates filaggrin and keratin K1, which maintains hydration of the stratum corneum, and hence the cutaneous barrier function. This enzyme may also play a role in hair follicle formation. This gene exists in a cluster with four other paralogous genes. [provided by RefSeq, Jul 2008]

PADI1 links:

Genome browser will be placed here

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=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI1	NM_013358.3 link	c.1459-121T>C		intron_variant	Intron 12 of 15	ENST00000375471.5	NP_037490.2	Q9ULC6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI1	ENST00000375471.5 link	c.1459-121T>C		intron_variant	Intron 12 of 15	1	NM_013358.3	ENSP00000364620.4		Q9ULC6

Frequencies

GnomAD3 genomes

AF:

0.514

AC:

78000

AN:

151844

Hom.:

20419

Cov.:

show subpopulations

Gnomad AFR

AF:

0.599

Gnomad AMI

AF:

0.647

Gnomad AMR

AF:

0.435

Gnomad ASJ

AF:

0.454

Gnomad EAS

AF:

0.429

Gnomad SAS

AF:

0.589

Gnomad FIN

AF:

0.450

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.493

Gnomad OTH

AF:

0.492

GnomAD4 exome

AF:

0.481

AC:

137790

AN:

286206

Hom.:

33747

AF XY:

0.481

AC XY:

70541

AN XY:

146554

show subpopulations

African (AFR)

AF:

0.586

AC:

4456

AN:

7606

American (AMR)

AF:

0.388

AC:

3115

AN:

8028

Ashkenazi Jewish (ASJ)

AF:

0.443

AC:

4222

AN:

9540

East Asian (EAS)

AF:

0.392

AC:

9046

AN:

23056

South Asian (SAS)

AF:

0.543

AC:

4595

AN:

8466

European-Finnish (FIN)

AF:

0.460

AC:

15120

AN:

32872

Middle Eastern (MID)

AF:

0.478

AC:

764

AN:

1598

European-Non Finnish (NFE)

AF:

0.494

AC:

87810

AN:

177606

Other (OTH)

AF:

0.497

AC:

8662

AN:

17434

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

3435

6869

10304

13738

17173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.514

AC:

78096

AN:

151962

Hom.:

20463

Cov.:

AF XY:

0.513

AC XY:

38080

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.600

AC:

24846

AN:

41436

American (AMR)

AF:

0.435

AC:

6643

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.454

AC:

1575

AN:

3466

East Asian (EAS)

AF:

0.429

AC:

2203

AN:

5140

South Asian (SAS)

AF:

0.590

AC:

2836

AN:

4810

European-Finnish (FIN)

AF:

0.450

AC:

4745

AN:

10556

Middle Eastern (MID)

AF:

0.469

AC:

138

AN:

294

European-Non Finnish (NFE)

AF:

0.492

AC:

33468

AN:

67958

Other (OTH)

AF:

0.498

AC:

1052

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1995

3990

5984

7979

9974

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.497

Hom.:

31579

Bravo

AF:

0.511

Asia WGS

AF:

0.554

AC:

1928

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.11

(source)

DANN

Benign

0.66

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs2977310

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