rs7538876

Variant names:

• chr1-17395867-G-A
• rs7538876
• NM_207421.4:c.1618+204G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_207421.4(PADI6):​c.1618+204G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 152,052 control chromosomes in the GnomAD database, including 10,202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.36 (10202 hom., cov: 33)
• Consequence: PADI6 NM_207421.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.501
• Publications: 61 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 1-17395867-G-A is Benign according to our data. Variant chr1-17395867-G-A is described in ClinVar as Benign. ClinVar VariationId is 704516.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PADI6	NM_207421.4	c.1618+204G>A		intron_variant	Intron 13 of 15	ENST00000619609.1	NP_997304.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PADI6	ENST00000619609.1	c.1618+204G>A		intron_variant	Intron 13 of 15	1	NM_207421.4	ENSP00000483125.1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55279 AN: 151932 Hom.: 10197 Cov.: 33

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.364 AC: 55315 AN: 152052 Hom.: 10202 Cov.: 33 AF XY: 0.369 AC XY: 27393 AN XY: 74330

African (AFR) AF: 0.357 AC: 14826 AN: 41474

American (AMR) AF: 0.376 AC: 5751 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 861 AN: 3470

East Asian (EAS) AF: 0.169 AC: 872 AN: 5154

South Asian (SAS) AF: 0.394 AC: 1900 AN: 4822

European-Finnish (FIN) AF: 0.422 AC: 4457 AN: 10564

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.377 AC: 25644 AN: 67970

Other (OTH) AF: 0.339 AC: 715 AN: 2112

Alfa AF: 0.365 Hom.: 45073

Bravo AF: 0.355

Asia WGS AF: 0.284 AC: 988 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 02, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.67
DANN	Benign	0.35
PhyloP100		-0.50

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: rs7538876; hg19: chr1-17722363;