rs190093444

Variant names:

• chr1-113837699-C-T
• rs190093444
• NM_015967.8:c.1701G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_015967.8(PTPN22):​c.1701G>A​(p.Leu567Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000207 in 1,606,526 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (2 hom.)
• Consequence: PTPN22 NM_015967.8 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:2
• Conservation: PhyloP100: 0.289
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 1-113837699-C-T is Benign according to our data. Variant chr1-113837699-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1285146.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.289 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 Unknown,AR gene

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.1701G>A	p.Leu567Leu	synonymous	Exon 13 of 21	NP_057051.4
	PTPN22	NM_001308297.2		c.1629G>A	p.Leu543Leu	synonymous	Exon 12 of 20	NP_001295226.2	F5H2S8
	PTPN22	NM_001193431.3		c.1701G>A	p.Leu567Leu	synonymous	Exon 13 of 21	NP_001180360.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN22	ENST00000359785.10	TSL:1 MANE Select	c.1701G>A	p.Leu567Leu	synonymous	Exon 13 of 21	ENSP00000352833.5	A0A0B4J1S7
	PTPN22	ENST00000420377.6	TSL:1	c.1701G>A	p.Leu567Leu	synonymous	Exon 13 of 20	ENSP00000388229.2	E9PMT0
	PTPN22	ENST00000538253.5	TSL:1	c.1629G>A	p.Leu543Leu	synonymous	Exon 12 of 20	ENSP00000439372.2	F5H2S8

Frequencies

GnomAD3 genomes AF: 0.000283 AC: 43 AN: 151996 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00617

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000672 AC: 169 AN: 251338 AF XY: 0.000699

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00799

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000199 AC: 290 AN: 1454412 Hom.: 2 Cov.: 31 AF XY: 0.000243 AC XY: 176 AN XY: 724084

African (AFR) AF: 0.000120 AC: 4 AN: 33326

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00482 AC: 191 AN: 39650

South Asian (SAS) AF: 0.000801 AC: 69 AN: 86104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1105222

Other (OTH) AF: 0.000399 AC: 24 AN: 60150

GnomAD4 genome AF: 0.000283 AC: 43 AN: 152114 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74358

African (AFR) AF: 0.000217 AC: 9 AN: 41496

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00618 AC: 32 AN: 5178

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000151 Hom.: 0

Bravo AF: 0.000450

Asia WGS AF: 0.00231 AC: 8 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.0
DANN	Benign	0.51
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism

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: rs190093444; hg19: chr1-114380321;