rs1378942

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_004383.3(CSK):c.-66+2306C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.434 (AC=66,036) in the gnomAD database across 152,054 control chromosomes, including 18,755 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.652. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 18755 hom., cov: 32)

Consequence

CSK
NM_004383.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0300

Publications

213 publications found

Variant links:

Genes affected

CSK (HGNC:2444): (C-terminal Src kinase) The protein encoded by this gene is involved in multiple pathways, including the regulation of Src family kinases. It plays an important role in T-cell activation through its association with the protein encoded by the protein tyrosine phosphatase, non-receptor type 22 (PTPN22) gene. This protein also phosphorylates C-terminal tyrosine residues on multiple substrates, including the protein encoded by the SRC proto-oncogene, non-receptor tyrosine kinase gene. Phosphorylation suppresses the kinase activity of the Src family tyrosine kinases. An intronic polymorphism (rs34933034) in this gene has been found to affect B-cell activation and is associated with systemic lupus erythematosus (SLE). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017]

CSK links:

ENSG00000299491 (HGNC:):

ENSG00000299491 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_004383.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

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

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.6516 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_004383.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CSK	NM_004383.3	MANE Select	c.-66+2306C>A	intron	N/A	NP_004374.1	B2R6Q4
CSK	NM_001127190.2		c.-66+2306C>A	intron	N/A	NP_001120662.1	P41240
CSK	NM_001387089.1		c.-87+2306C>A	intron	N/A	NP_001374018.1	B2R6Q4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CSK	ENST00000220003.14	TSL:1 MANE Select	c.-66+2306C>A	intron	N/A	ENSP00000220003.9	P41240
CSK	ENST00000563894.1	TSL:1	n.217+2306C>A	intron	N/A
CSK	ENST00000439220.6	TSL:2	c.-66+2306C>A	intron	N/A	ENSP00000414764.2	P41240

Frequencies

GnomAD3 genomes

AF:

0.435

AC:

66060

AN:

151936

Hom.:

18762

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.359

Gnomad ASJ

AF:

0.562

Gnomad EAS

AF:

0.175

Gnomad SAS

AF:

0.199

Gnomad FIN

AF:

0.550

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.657

Gnomad OTH

AF:

0.453

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

GnomAD4 genome

AF:

0.434

AC:

66036

AN:

152054

Hom.:

18755

Cov.:

AF XY:

0.421

AC XY:

31275

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.116

AC:

4800

AN:

41480

American (AMR)

AF:

0.358

AC:

5472

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.562

AC:

1949

AN:

3470

East Asian (EAS)

AF:

0.175

AC:

904

AN:

5174

South Asian (SAS)

AF:

0.197

AC:

950

AN:

4816

European-Finnish (FIN)

AF:

0.550

AC:

5808

AN:

10556

Middle Eastern (MID)

AF:

0.544

AC:

160

AN:

294

European-Non Finnish (NFE)

AF:

0.657

AC:

44632

AN:

67964

Other (OTH)

AF:

0.449

AC:

945

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1458

2917

4375

5834

7292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

572

1144

1716

2288

2860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.571

Hom.:

86040

Bravo

AF:

0.414

Asia WGS

AF:

0.166

AC:

581

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.205

AC:

25089

AN:

122680

Turkish Variome

AF:

0.505

AC:

780

AN:

1544

Hom.:

202

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.157

AC:

1407

AN:

8960

Hom.:

117

ABraOM SABE-WGS-1171

AF:

0.450

AC:

1054

AN:

2342

Hom.:

267

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.3

(source)

DANN

Benign

0.46

PhyloP100

-0.030

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over