15-74785026-C-G

Variant names:

• chr15-74785026-C-G
• NM_004383.3:c.-66+2306C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004383.3(CSK):​c.-66+2306C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: CSK NM_004383.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSK	NM_004383.3	c.-66+2306C>G		intron_variant	Intron 1 of 12	ENST00000220003.14	NP_004374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSK	ENST00000220003.14	c.-66+2306C>G		intron_variant	Intron 1 of 12	1	NM_004383.3	ENSP00000220003.9

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-75077367;