1-113839403-G-T

Variant names:

• chr1-113839403-G-T
• rs974404
• NM_015967.8:c.916-783C>A

Variant summary

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

The NM_015967.8(PTPN22):​c.916-783C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 144,036 control chromosomes in the GnomAD database, including 23,911 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 0.58 (23911 hom., cov: 27)
• Consequence: PTPN22 NM_015967.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN22	NM_015967.8	MANE Select	c.916-783C>A		intron	N/A	NP_057051.4
	PTPN22	NM_001308297.2		c.844-783C>A		intron	N/A	NP_001295226.2	F5H2S8
	PTPN22	NM_001193431.3		c.916-783C>A		intron	N/A	NP_001180360.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN22	ENST00000359785.10	TSL:1 MANE Select	c.916-783C>A		intron	N/A	ENSP00000352833.5	A0A0B4J1S7
	PTPN22	ENST00000420377.6	TSL:1	c.916-783C>A		intron	N/A	ENSP00000388229.2	E9PMT0
	PTPN22	ENST00000538253.5	TSL:1	c.844-783C>A		intron	N/A	ENSP00000439372.2	F5H2S8

Frequencies

GnomAD3 genomes AF: 0.579 AC: 83363 AN: 143968 Hom.: 23899 Cov.: 27

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.579 AC: 83413 AN: 144036 Hom.: 23911 Cov.: 27 AF XY: 0.575 AC XY: 40214 AN XY: 69986

African (AFR) AF: 0.665 AC: 26075 AN: 39208

American (AMR) AF: 0.477 AC: 6710 AN: 14058

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2074 AN: 3380

East Asian (EAS) AF: 0.175 AC: 822 AN: 4698

South Asian (SAS) AF: 0.662 AC: 3089 AN: 4664

European-Finnish (FIN) AF: 0.516 AC: 4704 AN: 9118

Middle Eastern (MID) AF: 0.635 AC: 174 AN: 274

European-Non Finnish (NFE) AF: 0.579 AC: 38107 AN: 65766

Other (OTH) AF: 0.567 AC: 1125 AN: 1984

Alfa AF: 0.142 Hom.: 353

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.047
DANN	Benign	0.37
PhyloP100		0.0
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: rs974404; hg19: chr1-114382025;