rs10488947

chr4-10502128-A-G

Variant summary

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

The NM_052964.4(CLNK):c.985-717T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,124 control chromosomes in the GnomAD database, including 2,016 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 0.12 (2016 hom., cov: 32)
• Consequence: CLNK NM_052964.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLNK	NM_052964.4	c.985-717T>C		intron_variant		ENST00000226951.11
LOC105374482	XR_925387.4	n.261+5573A>G		intron_variant, non_coding_transcript_variant
CLNK	XM_011513775.3	c.1030-717T>C		intron_variant
CLNK	XM_017007684.2	c.1030-717T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLNK	ENST00000226951.11	c.985-717T>C		intron_variant		1	NM_052964.4	P1
	ENST00000663264.1	n.97-28006A>G		intron_variant, non_coding_transcript_variant
CLNK	ENST00000515667.5	c.199-717T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18969 AN: 152006 Hom.: 2011 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0787

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.0927

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0439

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.125 AC: 18989 AN: 152124 Hom.: 2016 Cov.: 32 AF XY: 0.128 AC XY: 9493 AN XY: 74354

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.0786

Gnomad4 ASJ AF: 0.0233

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.0930

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.0439

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0544 Hom.: 743

Bravo AF: 0.130

Asia WGS AF: 0.171 AC: 598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.3
Dann	Benign	0.89

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: rs10488947; hg19: chr4-10503752;