chr1-113814041-A-G

Variant names:

• chr1-113814041-A-G
• rs3811021
• NM_015967.8:c.*864T>C

Variant summary

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

The NM_015967.8(PTPN22):​c.*864T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,316 control chromosomes in the GnomAD database, including 2,085 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 0.16 (2085 hom., cov: 33)
  • Exomes 𝑓: 0.098 (0 hom.)
• Consequence: PTPN22 NM_015967.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186
• Publications: 48 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).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN22	NM_015967.8	MANE Select	c.*864T>C		3_prime_UTR	Exon 21 of 21	NP_057051.4
	PTPN22	NM_001308297.2		c.*864T>C		3_prime_UTR	Exon 20 of 20	NP_001295226.2
	PTPN22	NM_001193431.3		c.*864T>C		3_prime_UTR	Exon 21 of 21	NP_001180360.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN22	ENST00000359785.10	TSL:1 MANE Select	c.*864T>C		3_prime_UTR	Exon 21 of 21	ENSP00000352833.5
	PTPN22	ENST00000538253.5	TSL:1	c.*864T>C		3_prime_UTR	Exon 20 of 20	ENSP00000439372.2
	PTPN22	ENST00000528414.5	TSL:1	c.*864T>C		3_prime_UTR	Exon 19 of 19	ENSP00000435176.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23620 AN: 152076 Hom.: 2084 Cov.: 33

Gnomad AFR AF: 0.0813

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.0984 AC: 12 AN: 122 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 6 AN XY: 72

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.0984 AC: 12 AN: 122

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.155 AC: 23630 AN: 152194 Hom.: 2085 Cov.: 33 AF XY: 0.156 AC XY: 11628 AN XY: 74400

African (AFR) AF: 0.0813 AC: 3378 AN: 41562

American (AMR) AF: 0.169 AC: 2591 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 536 AN: 3468

East Asian (EAS) AF: 0.229 AC: 1186 AN: 5184

South Asian (SAS) AF: 0.118 AC: 569 AN: 4828

European-Finnish (FIN) AF: 0.197 AC: 2090 AN: 10594

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12689 AN: 67946

Other (OTH) AF: 0.164 AC: 347 AN: 2114

Alfa AF: 0.177 Hom.: 3041

Bravo AF: 0.152

Asia WGS AF: 0.191 AC: 659 AN: 3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.6
DANN	Benign	0.65
PhyloP100		0.19
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: rs3811021; hg19: chr1-114356663;