Variant 4-10540556-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_052964.4(CLNK):c.540G>A(p.Pro180=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000577 in 1,613,870 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00059 ( 2 hom. )

Consequence

CLNK
NM_052964.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.90

Variant links:

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]

CLNK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP6

Variant 4-10540556-C-T is Benign according to our data. Variant chr4-10540556-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2654672.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CLNK	NM_052964.4 linkuse as main transcript	c.540G>A	p.Pro180=	synonymous_variant	11/19	ENST00000226951.11
CLNK	XM_011513775.3 linkuse as main transcript	c.585G>A	p.Pro195=	synonymous_variant	11/19
CLNK	XM_017007684.2 linkuse as main transcript	c.585G>A	p.Pro195=	synonymous_variant	11/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLNK	ENST00000226951.11 linkuse as main transcript	c.540G>A	p.Pro180=	synonymous_variant	11/19	1	NM_052964.4	P1	Q7Z7G1-1
CLNK	ENST00000507719.1 linkuse as main transcript	c.414G>A	p.Pro138=	synonymous_variant	11/13	1			Q7Z7G1-2

Frequencies

GnomAD3 genomes

AF:

0.000421

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000494

AC:

123

AN:

249208

Hom.:

AF XY:

0.000599

AC XY:

AN XY:

135196

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000575

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.000595

AC:

869

AN:

1461628

Hom.:

Cov.:

AF XY:

0.000664

AC XY:

483

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00111

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000587

Gnomad4 OTH exome

AF:

0.000580

GnomAD4 genome

AF:

0.000414

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000706

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000702

Hom.:

Bravo

AF:

0.000502

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

CLNK: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

Cadd

Benign

0.076

Dann

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.22

Position offset: 48

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over