rs1378942

chr15-74785026-C-Achr15-74785026-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 frequency of 0.434 in 152,054 control chromosomes in the GnomAD database, including 18,755 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 (18755 hom., 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSK	NM_004383.3	c.-66+2306C>A		intron_variant		ENST00000220003.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSK	ENST00000220003.14	c.-66+2306C>A		intron_variant		1	NM_004383.3	P1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66060 AN: 151936 Hom.: 18762 Cov.: 32

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.: 32 AF XY: 0.421 AC XY: 31275 AN XY: 74310

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.657

Gnomad4 OTH AF: 0.449

Alfa AF: 0.581 Hom.: 29902

Bravo AF: 0.414

Asia WGS AF: 0.166 AC: 581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.3
Dann	Benign	0.46

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

LitVar

Other links and lift over

dbSNP: rs1378942; hg19: chr15-75077367;