rs7555634

Variant names:

• chr1-113824494-C-T
• rs7555634
• ENST00000359785.10:c.2281+648G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000359785.10(PTPN22):​c.2281+648G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 152,088 control chromosomes in the GnomAD database, including 25,328 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 0.57 (25328 hom., cov: 33)
• Consequence: PTPN22 ENST00000359785.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.583
• Publications: 17 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=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN22	NM_015967.8	c.2281+648G>A		intron_variant	Intron 19 of 20		NP_057051.4
PTPN22	NM_001308297.2	c.2209+648G>A		intron_variant	Intron 18 of 19		NP_001295226.2
PTPN22	NM_001193431.3	c.2197+648G>A		intron_variant	Intron 19 of 20		NP_001180360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10	c.2281+648G>A		intron_variant	Intron 19 of 20	1		ENSP00000352833.5

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86209 AN: 151970 Hom.: 25302 Cov.: 33

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.551

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.567 AC: 86288 AN: 152088 Hom.: 25328 Cov.: 33 AF XY: 0.562 AC XY: 41740 AN XY: 74332

African (AFR) AF: 0.664 AC: 27569 AN: 41502

American (AMR) AF: 0.454 AC: 6931 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2113 AN: 3470

East Asian (EAS) AF: 0.160 AC: 829 AN: 5172

South Asian (SAS) AF: 0.651 AC: 3147 AN: 4834

European-Finnish (FIN) AF: 0.489 AC: 5152 AN: 10542

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38680 AN: 67972

Other (OTH) AF: 0.547 AC: 1155 AN: 2112

Alfa AF: 0.576 Hom.: 9426

Bravo AF: 0.560

Asia WGS AF: 0.438 AC: 1524 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	14
DANN	Benign	0.59
PhyloP100		0.58
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: rs7555634; hg19: chr1-114367116;