Genetic Variant ENST00000359785.10:c.541-117G>A (chr1-113855166-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000359785.10(PTPN22):c.541-117G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 862,672 control chromosomes in the GnomAD database, including 13,988 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 ( 2113 hom., cov: 32)

Exomes 𝑓: 0.18 ( 11875 hom. )

Consequence

PTPN22
ENST00000359785.10 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.25

Publications

5 publications found

Variant links:

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]

PTPN22 links:

AP4B1-AS1 (HGNC:44114): (AP4B1 antisense RNA 1)

AP4B1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
PTPN22	NM_015967.8 link	c.541-117G>A	intron_variant	Intron 7 of 20	NP_057051.4	Q9Y2R2B4DZW8
PTPN22	NM_001308297.2 link	c.469-117G>A	intron_variant	Intron 6 of 19	NP_001295226.2	Q9Y2R2G3K0T4
PTPN22	NM_001193431.3 link	c.541-117G>A	intron_variant	Intron 7 of 20	NP_001180360.2	Q9Y2R2-4B4DZW8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN22	ENST00000359785.10 link	c.541-117G>A		intron_variant	Intron 7 of 20	1		ENSP00000352833.5		A0A0B4J1S7

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23759

AN:

151988

Hom.:

2112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0818

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.230

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.198

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.162

GnomAD4 exome

AF:

0.178

AC:

126215

AN:

710566

Hom.:

11875

AF XY:

0.175

AC XY:

64186

AN XY:

366260

show subpopulations

African (AFR)

AF:

0.0766

AC:

1338

AN:

17476

American (AMR)

AF:

0.142

AC:

3495

AN:

24562

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

2456

AN:

15944

East Asian (EAS)

AF:

0.209

AC:

6972

AN:

33410

South Asian (SAS)

AF:

0.116

AC:

6180

AN:

53444

European-Finnish (FIN)

AF:

0.186

AC:

7606

AN:

40908

Middle Eastern (MID)

AF:

0.127

AC:

360

AN:

2840

European-Non Finnish (NFE)

AF:

0.189

AC:

91931

AN:

487500

Other (OTH)

AF:

0.170

AC:

5877

AN:

34482

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

4989

9978

14968

19957

24946

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.156

AC:

23769

AN:

152106

Hom.:

2113

Cov.:

AF XY:

0.157

AC XY:

11688

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.0819

AC:

3398

AN:

41512

American (AMR)

AF:

0.169

AC:

2586

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

544

AN:

3468

East Asian (EAS)

AF:

0.230

AC:

1190

AN:

5174

South Asian (SAS)

AF:

0.117

AC:

566

AN:

4820

European-Finnish (FIN)

AF:

0.198

AC:

2092

AN:

10572

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.188

AC:

12802

AN:

67992

Other (OTH)

AF:

0.166

AC:

348

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

989

1978

2966

3955

4944

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.168

Hom.:

921

Bravo

AF:

0.153

Asia WGS

AF:

0.195

AC:

678

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.79

(source)

DANN

Benign

0.51

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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ENST00000359785.10:c.541-117G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over