rs34209542

Variant names:

• chr1-113829902-A-G
• rs34209542
• ENST00000359785.10:c.2134+47T>C

Variant summary

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

The ENST00000359785.10(PTPN22):​c.2134+47T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 1,493,702 control chromosomes in the GnomAD database, including 439 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 0.017 (33 hom., cov: 32)
  • Exomes 𝑓: 0.022 (406 hom.)
• Consequence: PTPN22 ENST00000359785.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174
• Publications: 6 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=-0.83).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.017 (2581/152070) while in subpopulation NFE AF = 0.0257 (1746/67960). AF 95% confidence interval is 0.0247. There are 33 homozygotes in GnomAd4. There are 1204 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 Unknown,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.2134+47T>C		intron_variant	Intron 17 of 20		NP_057051.4
PTPN22	NM_001308297.2	c.2062+47T>C		intron_variant	Intron 16 of 19		NP_001295226.2
PTPN22	NM_001193431.3	c.2050+47T>C		intron_variant	Intron 17 of 20		NP_001180360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.2134+47T>C		intron_variant	Intron 17 of 20	1		ENSP00000352833.5

Frequencies

GnomAD3 genomes AF: 0.0170 AC: 2583 AN: 151952 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.00488

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.0162

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0257

Gnomad OTH AF: 0.0226

GnomAD2 exomes AF: 0.0184 AC: 4496 AN: 244244 AF XY: 0.0192

Gnomad AFR exome AF: 0.00470

Gnomad AMR exome AF: 0.0152

Gnomad ASJ exome AF: 0.0161

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.0228

Gnomad NFE exome AF: 0.0237

Gnomad OTH exome AF: 0.0199

GnomAD4 exome AF: 0.0224 AC: 30055 AN: 1341632 Hom.: 406 Cov.: 22 AF XY: 0.0221 AC XY: 14890 AN XY: 673032

African (AFR) AF: 0.00383 AC: 117 AN: 30582

American (AMR) AF: 0.0153 AC: 676 AN: 44104

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 416 AN: 25396

East Asian (EAS) AF: 0.0000771 AC: 3 AN: 38912

South Asian (SAS) AF: 0.0170 AC: 1412 AN: 83116

European-Finnish (FIN) AF: 0.0199 AC: 1061 AN: 53250

Middle Eastern (MID) AF: 0.0130 AC: 72 AN: 5536

European-Non Finnish (NFE) AF: 0.0251 AC: 25232 AN: 1004384

Other (OTH) AF: 0.0189 AC: 1066 AN: 56352

GnomAD4 genome AF: 0.0170 AC: 2581 AN: 152070 Hom.: 33 Cov.: 32 AF XY: 0.0162 AC XY: 1204 AN XY: 74338

African (AFR) AF: 0.00487 AC: 202 AN: 41476

American (AMR) AF: 0.0162 AC: 248 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0162 AC: 56 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.0122 AC: 59 AN: 4820

European-Finnish (FIN) AF: 0.0202 AC: 214 AN: 10588

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0257 AC: 1746 AN: 67960

Other (OTH) AF: 0.0223 AC: 47 AN: 2104

Alfa AF: 0.0213 Hom.: 15

Bravo AF: 0.0158

Asia WGS AF: 0.00549 AC: 19 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.63
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs34209542; hg19: chr1-114372524;