NM_015967.8:c.541-441G>A

Variant names:

• chr1-113855490-C-T
• rs34122108
• NM_015967.8:c.541-441G>A

Variant summary

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

The NM_015967.8(PTPN22):​c.541-441G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 117,328 control chromosomes in the GnomAD database, including 1,783 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 0.18 (1783 hom., cov: 21)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.738
• Publications: 5 publications found

Genes affected

PTPN22 (HGNC:9652): (protein tyrosine phosphatase non-receptor type 22) This gene encodes of member of the non-receptor class 4 subfamily of the protein-tyrosine phosphatase family. The encoded protein is a lymphoid-specific intracellular phosphatase that associates with the molecular adapter protein CBL and may be involved in regulating CBL function in the T-cell receptor signaling pathway. Mutations in this gene may be associated with a range of autoimmune disorders including Type 1 Diabetes, rheumatoid arthritis, systemic lupus erythematosus and Graves' disease. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Mar 2009]

AP4B1-AS1 (HGNC:44114): (AP4B1 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015967.8. 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
	PTPN22	NM_015967.8	MANE Select	c.541-441G>A		intron	N/A	NP_057051.4
	PTPN22	NM_001308297.2		c.469-441G>A		intron	N/A	NP_001295226.2
	PTPN22	NM_001193431.3		c.541-441G>A		intron	N/A	NP_001180360.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN22	ENST00000359785.10	TSL:1 MANE Select	c.541-441G>A		intron	N/A	ENSP00000352833.5
	PTPN22	ENST00000420377.6	TSL:1	c.541-441G>A		intron	N/A	ENSP00000388229.2
	PTPN22	ENST00000538253.5	TSL:1	c.469-441G>A		intron	N/A	ENSP00000439372.2

Frequencies

GnomAD3 genomes AF: 0.177 AC: 20783 AN: 117324 Hom.: 1783 Cov.: 21

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.189

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.177 AC: 20781 AN: 117328 Hom.: 1783 Cov.: 21 AF XY: 0.181 AC XY: 9852 AN XY: 54430

African (AFR) AF: 0.104 AC: 2766 AN: 26536

American (AMR) AF: 0.219 AC: 2114 AN: 9670

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 525 AN: 3258

East Asian (EAS) AF: 0.231 AC: 1022 AN: 4418

South Asian (SAS) AF: 0.125 AC: 449 AN: 3586

European-Finnish (FIN) AF: 0.249 AC: 1364 AN: 5472

Middle Eastern (MID) AF: 0.172 AC: 30 AN: 174

European-Non Finnish (NFE) AF: 0.194 AC: 12033 AN: 61868

Other (OTH) AF: 0.190 AC: 287 AN: 1510

Alfa AF: 0.0644 Hom.: 86

Bravo AF: 0.152

Asia WGS AF: 0.192 AC: 667 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.86
DANN	Benign	0.46
PhyloP100		-0.74
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

Other links and lift over

dbSNP: rs34122108; hg19: chr1-114398112;