chr4-10735030-T-C

Variant names:

• chr4-10735030-T-C
• rs6831297
• XM_011513775.3:c.-500A>G

Variant summary

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

The XM_011513775.3(CLNK):​c.-500A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,082 control chromosomes in the GnomAD database, including 11,475 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 0.36 (11475 hom., cov: 33)
• Consequence: CLNK XM_011513775.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLNK	XM_011513775.3	c.-500A>G		upstream_gene_variant			XP_011512077.1
CLNK	XM_017007684.2	c.-500A>G		upstream_gene_variant			XP_016863173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54272 AN: 151966 Hom.: 11430 Cov.: 33

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.357 AC: 54359 AN: 152082 Hom.: 11475 Cov.: 33 AF XY: 0.356 AC XY: 26475 AN XY: 74356

Gnomad4 AFR AF: 0.597

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.356

Alfa AF: 0.308 Hom.: 1396

Bravo AF: 0.361

Asia WGS AF: 0.358 AC: 1247 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	1.1
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6831297; hg19: chr4-10736654;