rs2526839

Variant names:

• chr1-17390817-A-C
• rs2526839
• NM_207421.4:c.963-1297A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-17390817-A-C
• chr1-17390817-A-G

Variant summary

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

The NM_207421.4(PADI6):​c.963-1297A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,042 control chromosomes in the GnomAD database, including 7,132 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 0.30 (7132 hom., cov: 32)
• Consequence: PADI6 NM_207421.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.464
• Publications: 8 publications found

Genes affected

PADI6 (HGNC:20449): (peptidyl arginine deiminase 6) 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. This protein may play a role in cytoskeletal reorganization in the egg and in early embryo development. [provided by RefSeq, Sep 2012]

PADI6 Gene-Disease associations (from GenCC):

• preimplantation embryonic lethality 2

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI6	NM_207421.4	c.963-1297A>C		intron_variant	Intron 8 of 15	ENST00000619609.1	NP_997304.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI6	ENST00000619609.1	c.963-1297A>C		intron_variant	Intron 8 of 15	1	NM_207421.4	ENSP00000483125.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45464 AN: 151920 Hom.: 7123 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.299 AC: 45504 AN: 152042 Hom.: 7132 Cov.: 32 AF XY: 0.293 AC XY: 21809 AN XY: 74316

African (AFR) AF: 0.371 AC: 15382 AN: 41456

American (AMR) AF: 0.288 AC: 4394 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1041 AN: 3472

East Asian (EAS) AF: 0.351 AC: 1813 AN: 5158

South Asian (SAS) AF: 0.274 AC: 1318 AN: 4816

European-Finnish (FIN) AF: 0.181 AC: 1921 AN: 10602

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18522 AN: 67974

Other (OTH) AF: 0.324 AC: 685 AN: 2112

Alfa AF: 0.263 Hom.: 3740

Bravo AF: 0.315

Asia WGS AF: 0.335 AC: 1165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.59
PhyloP100		0.46

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: rs2526839; hg19: chr1-17717312;