4-10725229-C-T

Position:

• chr4-10725229-C-T

Variant summary

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

The XM_011513775.3(CLNK):​c.3+9299G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 137,804 control chromosomes in the GnomAD database, including 6,697 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 0.32 (6697 hom., cov: 31)
• Consequence: CLNK XM_011513775.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLNK	XM_011513775.3	c.3+9299G>A		intron_variant			XP_011512077.1
CLNK	XM_017007684.2	c.3+9299G>A		intron_variant			XP_016863173.1
		n.10725229C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.324 AC: 44598 AN: 137706 Hom.: 6689 Cov.: 31

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.176

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.324 AC: 44635 AN: 137804 Hom.: 6697 Cov.: 31 AF XY: 0.318 AC XY: 21325 AN XY: 67134

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.329

Alfa AF: 0.469 Hom.: 34638

Bravo AF: 0.300

Asia WGS AF: 0.244 AC: 846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.48

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16872571; hg19: chr4-10726853;