chr1-113819496-A-T

Variant names:

• chr1-113819496-A-T
• rs34639107
• ENST00000420377.6:c.*52T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000420377.6(PTPN22):​c.*52T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,035,384 control chromosomes in the GnomAD database, including 215 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 0.023 (50 hom., cov: 32)
  • Exomes 𝑓: 0.016 (165 hom.)
• Consequence: PTPN22 ENST00000420377.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.382
• Publications: 2 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=-0.87).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0229 (3495/152330) while in subpopulation AFR AF = 0.0402 (1672/41570). AF 95% confidence interval is 0.0386. There are 50 homozygotes in GnomAd4. There are 1677 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 50 Unknown,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000420377.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN22	NM_015967.8	MANE Select	c.2359+81T>A		intron	N/A	NP_057051.4
	PTPN22	NM_001308297.2		c.2287+81T>A		intron	N/A	NP_001295226.2
	PTPN22	NM_001193431.3		c.2275+81T>A		intron	N/A	NP_001180360.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN22	ENST00000420377.6	TSL:1	c.*52T>A		3_prime_UTR	Exon 20 of 20	ENSP00000388229.2
	PTPN22	ENST00000359785.10	TSL:1 MANE Select	c.2359+81T>A		intron	N/A	ENSP00000352833.5
	PTPN22	ENST00000538253.5	TSL:1	c.2287+81T>A		intron	N/A	ENSP00000439372.2

Frequencies

GnomAD3 genomes AF: 0.0230 AC: 3496 AN: 152212 Hom.: 50 Cov.: 32

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0173

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.00724

Gnomad FIN AF: 0.0277

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0158

Gnomad OTH AF: 0.0320

GnomAD4 exome AF: 0.0159 AC: 14044 AN: 883054 Hom.: 165 Cov.: 11 AF XY: 0.0155 AC XY: 6977 AN XY: 449422

African (AFR) AF: 0.0400 AC: 821 AN: 20500

American (AMR) AF: 0.0145 AC: 407 AN: 27984

Ashkenazi Jewish (ASJ) AF: 0.0183 AC: 352 AN: 19220

East Asian (EAS) AF: 0.000843 AC: 29 AN: 34396

South Asian (SAS) AF: 0.00725 AC: 397 AN: 54744

European-Finnish (FIN) AF: 0.0262 AC: 1127 AN: 43090

Middle Eastern (MID) AF: 0.0213 AC: 75 AN: 3518

European-Non Finnish (NFE) AF: 0.0157 AC: 10056 AN: 640116

Other (OTH) AF: 0.0198 AC: 780 AN: 39486

GnomAD4 genome AF: 0.0229 AC: 3495 AN: 152330 Hom.: 50 Cov.: 32 AF XY: 0.0225 AC XY: 1677 AN XY: 74484

African (AFR) AF: 0.0402 AC: 1672 AN: 41570

American (AMR) AF: 0.0173 AC: 264 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 67 AN: 3470

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5192

South Asian (SAS) AF: 0.00704 AC: 34 AN: 4832

European-Finnish (FIN) AF: 0.0277 AC: 294 AN: 10616

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0158 AC: 1076 AN: 68024

Other (OTH) AF: 0.0317 AC: 67 AN: 2116

Alfa AF: 0.0220 Hom.: 2

Bravo AF: 0.0227

Asia WGS AF: 0.0190 AC: 65 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.70
PhyloP100		0.38
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: rs34639107; hg19: chr1-114362118;