rs2168518

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_004383.3(CSK):c.-66+6017G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 154,224 control chromosomes in the GnomAD database, including 19,040 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 0.43 ( 18771 hom., cov: 33)

Exomes 𝑓: 0.49 ( 269 hom. )

Consequence

CSK
NM_004383.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0180

Publications

61 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:

MIR4513 (HGNC:41855): (microRNA 4513) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR4513 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=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Variant Effect in Transcripts

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

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CSK	NM_004383.3	MANE Select	c.-66+6017G>A	intron	N/A	NP_004374.1	B2R6Q4
CSK	NM_001127190.2		c.-66+6017G>A	intron	N/A	NP_001120662.1	P41240
CSK	NM_001354988.2		c.-399+160G>A	intron	N/A	NP_001341917.1	P41240

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CSK	ENST00000220003.14	TSL:1 MANE Select	c.-66+6017G>A	intron	N/A	ENSP00000220003.9	P41240
CSK	ENST00000563894.1	TSL:1	n.217+6017G>A	intron	N/A
CSK	ENST00000439220.6	TSL:2	c.-66+6017G>A	intron	N/A	ENSP00000414764.2	P41240

Frequencies

GnomAD3 genomes

AF:

0.435

AC:

66101

AN:

152060

Hom.:

18778

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.459

Gnomad AMR

AF:

0.358

Gnomad ASJ

AF:

0.562

Gnomad EAS

AF:

0.175

Gnomad SAS

AF:

0.199

Gnomad FIN

AF:

0.551

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.657

Gnomad OTH

AF:

0.455

GnomAD2 exomes

AF:

0.708

AC:

269

AN:

380

AF XY:

0.703

show subpopulations

Gnomad ASJ exome

AF:

0.500

Gnomad FIN exome

AF:

0.750

Gnomad NFE exome

AF:

0.712

Gnomad OTH exome

AF:

0.600

GnomAD4 exome

AF:

0.487

AC:

996

AN:

2046

Hom.:

269

Cov.:

AF XY:

0.502

AC XY:

511

AN XY:

1018

show subpopulations

African (AFR)

AF:

0.206

AC:

AN:

American (AMR)

AF:

0.125

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.233

AC:

AN:

European-Finnish (FIN)

AF:

0.875

AC:

AN:

Middle Eastern (MID)

AF:

0.514

AC:

779

AN:

1516

European-Non Finnish (NFE)

AF:

0.661

AC:

119

AN:

180

Other (OTH)

AF:

0.313

AC:

AN:

176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.434

AC:

66077

AN:

152178

Hom.:

18771

Cov.:

AF XY:

0.421

AC XY:

31296

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.116

AC:

4802

AN:

41534

American (AMR)

AF:

0.358

AC:

5471

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.562

AC:

1949

AN:

3470

East Asian (EAS)

AF:

0.175

AC:

908

AN:

5178

South Asian (SAS)

AF:

0.198

AC:

954

AN:

4830

European-Finnish (FIN)

AF:

0.551

AC:

5821

AN:

10574

Middle Eastern (MID)

AF:

0.545

AC:

159

AN:

292

European-Non Finnish (NFE)

AF:

0.657

AC:

44643

AN:

67982

Other (OTH)

AF:

0.450

AC:

952

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1558

3116

4674

6232

7790

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:

0.521

Hom.:

3515

Bravo

AF:

0.414

Asia WGS

AF:

0.165

AC:

580

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.1

(source)

DANN

Benign

0.87

PhyloP100

-0.018

PromoterAI

-0.018

Neutral

(source)

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over