chr1-17356837-T-G

Variant names:

• chr1-17356837-T-G
• rs1635565
• NM_012387.3:c.1558+378T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_012387.3(PADI4):​c.1558+378T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0010 (0 hom., cov: 26)
  • Failed GnomAD Quality Control
• Consequence: PADI4 NM_012387.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012387.3. 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
	PADI4	NM_012387.3	MANE Select	c.1558+378T>G		intron	N/A	NP_036519.2	Q9UM07

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PADI4	ENST00000375448.4	TSL:1 MANE Select	c.1558+378T>G		intron	N/A	ENSP00000364597.4	Q9UM07
	PADI4	ENST00000467001.1	TSL:5	n.459+378T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000993 AC: 143 AN: 144046 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.000840

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00113

Gnomad ASJ AF: 0.000583

Gnomad EAS AF: 0.000205

Gnomad SAS AF: 0.00135

Gnomad FIN AF: 0.000208

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.00126

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000999 AC: 144 AN: 144150 Hom.: 0 Cov.: 26 AF XY: 0.000714 AC XY: 50 AN XY: 70070

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000838 AC: 33 AN: 39380

American (AMR) AF: 0.00113 AC: 16 AN: 14140

Ashkenazi Jewish (ASJ) AF: 0.000583 AC: 2 AN: 3428

East Asian (EAS) AF: 0.000205 AC: 1 AN: 4872

South Asian (SAS) AF: 0.00158 AC: 7 AN: 4432

European-Finnish (FIN) AF: 0.000208 AC: 2 AN: 9606

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.00126 AC: 82 AN: 65112

Other (OTH) AF: 0.00 AC: 0 AN: 2014

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000713 Hom.: 1915

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.20
DANN	Benign	0.36
PhyloP100		-0.38

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: rs1635565;

hg19: chr1-17683332;