4-10490563-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_052964.4(CLNK):c.1191T>C(p.Ile397=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00533 in 1,595,612 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0054 (15 hom.)
• Consequence: CLNK NM_052964.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.182

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-10490563-A-G is Benign according to our data. Variant chr4-10490563-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2654671.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.182 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLNK	NM_052964.4	c.1191T>C	p.Ile397=	synonymous_variant	19/19	ENST00000226951.11
LOC105374482	XR_925387.4	n.83+1368A>G		intron_variant, non_coding_transcript_variant
CLNK	XM_011513775.3	c.1236T>C	p.Ile412=	synonymous_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLNK	ENST00000226951.11	c.1191T>C	p.Ile397=	synonymous_variant	19/19	1	NM_052964.4	P1
	ENST00000663264.1	n.96+33723A>G		intron_variant, non_coding_transcript_variant
CLNK	ENST00000515667.5	c.405T>C	p.Ile135=	synonymous_variant	5/5	3

Frequencies

GnomAD3 genomes AF: 0.00437 AC: 665 AN: 152172 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00989

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00655

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00445 AC: 971 AN: 218274 Hom.: 2 AF XY: 0.00440 AC XY: 517 AN XY: 117376

Gnomad AFR exome AF: 0.000978

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.000741

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00214

Gnomad FIN exome AF: 0.0110

Gnomad NFE exome AF: 0.00642

Gnomad OTH exome AF: 0.00253

GnomAD4 exome AF: 0.00543 AC: 7837 AN: 1443322 Hom.: 15 Cov.: 30 AF XY: 0.00522 AC XY: 3739 AN XY: 716234

Gnomad4 AFR exome AF: 0.000995

Gnomad4 AMR exome AF: 0.00132

Gnomad4 ASJ exome AF: 0.000970

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00207

Gnomad4 FIN exome AF: 0.0109

Gnomad4 NFE exome AF: 0.00609

Gnomad4 OTH exome AF: 0.00423

GnomAD4 genome AF: 0.00436 AC: 664 AN: 152290 Hom.: 1 Cov.: 33 AF XY: 0.00406 AC XY: 302 AN XY: 74460

Gnomad4 AFR AF: 0.00116

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00989

Gnomad4 NFE AF: 0.00656

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00547 Hom.: 0

Bravo AF: 0.00354

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

CLNK: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.1
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: rs189381725; hg19: chr4-10492187;