rs12233843

chr4-10653594-A-Gchr4-10653594-A-T

Variant summary

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

The NM_052964.4(CLNK):c.11+14265T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 152,014 control chromosomes in the GnomAD database, including 16,011 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 0.44 (16011 hom., cov: 32)
• Consequence: CLNK NM_052964.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

Genes affected

CLNK (HGNC:17438): (cytokine dependent hematopoietic cell linker) MIST is a member of the SLP76 family of adaptors (see LCP2, MIM 601603; BLNK, MIM 604515). MIST plays a role in the regulation of immunoreceptor signaling, including PLC-gamma (PLCG1; MIM 172420)-mediated B cell antigen receptor (BCR) signaling and FC-epsilon R1 (see FCER1A, MIM 147140)-mediated mast cell degranulation (Cao et al., 1999 [PubMed 10562326]; Goitsuka et al., 2000, 2001 [PubMed 10744659] [PubMed 11463797]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLNK	NM_052964.4	c.11+14265T>C		intron_variant		ENST00000226951.11
CLNK	XM_011513775.3	c.56+14265T>C		intron_variant
CLNK	XM_017007684.2	c.56+14265T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLNK	ENST00000226951.11	c.11+14265T>C		intron_variant		1	NM_052964.4	P1
CLNK	ENST00000507719.1	c.-241+2915T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67210 AN: 151896 Hom.: 16007 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.442 AC: 67220 AN: 152014 Hom.: 16011 Cov.: 32 AF XY: 0.442 AC XY: 32818 AN XY: 74308

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.466

Alfa AF: 0.519 Hom.: 28372

Bravo AF: 0.429

Asia WGS AF: 0.475 AC: 1644 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	6.1
Dann	Benign	0.73

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: rs12233843; hg19: chr4-10655218;