NM_004383.3:c.-66+2306C>A

Variant names:

• chr15-74785026-C-A
• rs1378942
• NM_004383.3:c.-66+2306C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 213 publications found

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]

ENSG00000299491 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSK	ENST00000220003.14	TSL:1 MANE Select	c.-66+2306C>A		intron	N/A	ENSP00000220003.9
	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

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

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

Alfa AF: 0.571 Hom.: 86040

Bravo AF: 0.414

Asia WGS AF: 0.166 AC: 581 AN: 3478

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
DANN	Benign	0.46
PhyloP100		-0.030
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1378942; hg19: chr15-75077367;