chr1-113855177-C-T

Variant names:

• chr1-113855177-C-T
• rs3789609
• NM_015967.8:c.541-128G>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.541-128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 757,308 control chromosomes in the GnomAD database, including 29,972 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 0.22 (4521 hom., cov: 31)
  • Exomes 𝑓: 0.28 (25451 hom.)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 10 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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.376 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.541-128G>A		intron	N/A	NP_057051.4
	PTPN22	NM_001308297.2		c.469-128G>A		intron	N/A	NP_001295226.2	F5H2S8
	PTPN22	NM_001193431.3		c.541-128G>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.541-128G>A		intron	N/A	ENSP00000352833.5	A0A0B4J1S7
	PTPN22	ENST00000420377.6	TSL:1	c.541-128G>A		intron	N/A	ENSP00000388229.2	E9PMT0
	PTPN22	ENST00000538253.5	TSL:1	c.469-128G>A		intron	N/A	ENSP00000439372.2	F5H2S8

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33062 AN: 152012 Hom.: 4522 Cov.: 31

Gnomad AFR AF: 0.0594

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.0936

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.247

GnomAD4 exome AF: 0.280 AC: 169432 AN: 605178 Hom.: 25451 AF XY: 0.286 AC XY: 89724 AN XY: 313996

African (AFR) AF: 0.0544 AC: 837 AN: 15376

American (AMR) AF: 0.239 AC: 5239 AN: 21952

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 4261 AN: 14974

East Asian (EAS) AF: 0.0861 AC: 2760 AN: 32068

South Asian (SAS) AF: 0.380 AC: 18499 AN: 48706

European-Finnish (FIN) AF: 0.250 AC: 9258 AN: 36986

Middle Eastern (MID) AF: 0.315 AC: 780 AN: 2476

European-Non Finnish (NFE) AF: 0.297 AC: 119211 AN: 401532

Other (OTH) AF: 0.276 AC: 8587 AN: 31108

GnomAD4 genome AF: 0.217 AC: 33068 AN: 152130 Hom.: 4521 Cov.: 31 AF XY: 0.218 AC XY: 16205 AN XY: 74374

African (AFR) AF: 0.0593 AC: 2460 AN: 41508

American (AMR) AF: 0.231 AC: 3528 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1032 AN: 3472

East Asian (EAS) AF: 0.0936 AC: 485 AN: 5182

South Asian (SAS) AF: 0.390 AC: 1881 AN: 4818

European-Finnish (FIN) AF: 0.249 AC: 2637 AN: 10588

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20162 AN: 67978

Other (OTH) AF: 0.246 AC: 520 AN: 2112

Alfa AF: 0.241 Hom.: 905

Bravo AF: 0.207

Asia WGS AF: 0.239 AC: 833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.87
DANN	Benign	0.48
PhyloP100		-1.6
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: rs3789609; hg19: chr1-114397799;