rs2977310

Variant names:

• chr1-17238495-T-C
• rs2977310
• NM_013358.3:c.1459-121T>C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 8 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013358.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI1	NM_013358.3	MANE Select	c.1459-121T>C		intron	N/A	NP_037490.2	Q9ULC6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI1	ENST00000375471.5	TSL:1 MANE Select	c.1459-121T>C		intron	N/A	ENSP00000364620.4	Q9ULC6

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78000 AN: 151844 Hom.: 20419 Cov.: 32

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

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

GnomAD4 genome AF: 0.514 AC: 78096 AN: 151962 Hom.: 20463 Cov.: 32 AF XY: 0.513 AC XY: 38080 AN XY: 74282

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.11
DANN	Benign	0.66
PhyloP100		-1.3
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2977310;

hg19: chr1-17564990;

COSMIC: COSV64938775;

COSMIC: COSV64938775;