NM_015967.8:c.916-4841T>C

Variant names:

• chr1-113843461-A-G
• rs2185827
• NM_015967.8:c.916-4841T>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.916-4841T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,038 control chromosomes in the GnomAD database, including 9,357 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 0.32 (9357 hom., cov: 32)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 13 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=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.53 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.916-4841T>C		intron	N/A	NP_057051.4
	PTPN22	NM_001308297.2		c.844-4841T>C		intron	N/A	NP_001295226.2
	PTPN22	NM_001193431.3		c.916-4841T>C		intron	N/A	NP_001180360.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN22	ENST00000359785.10	TSL:1 MANE Select	c.916-4841T>C		intron	N/A	ENSP00000352833.5
	PTPN22	ENST00000420377.6	TSL:1	c.916-4841T>C		intron	N/A	ENSP00000388229.2
	PTPN22	ENST00000538253.5	TSL:1	c.844-4841T>C		intron	N/A	ENSP00000439372.2

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48395 AN: 151920 Hom.: 9336 Cov.: 32

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.0649

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.319 AC: 48460 AN: 152038 Hom.: 9357 Cov.: 32 AF XY: 0.313 AC XY: 23243 AN XY: 74350

African (AFR) AF: 0.536 AC: 22217 AN: 41436

American (AMR) AF: 0.203 AC: 3098 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1013 AN: 3468

East Asian (EAS) AF: 0.0650 AC: 337 AN: 5182

South Asian (SAS) AF: 0.254 AC: 1223 AN: 4818

European-Finnish (FIN) AF: 0.210 AC: 2222 AN: 10578

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17446 AN: 67976

Other (OTH) AF: 0.267 AC: 562 AN: 2108

Alfa AF: 0.315 Hom.: 1097

Bravo AF: 0.322

Asia WGS AF: 0.178 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.94
PhyloP100		0.12
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: rs2185827; hg19: chr1-114386083;