Variant 4-10525848-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_052964.4(CLNK):c.724A>G(p.Ile242Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,578,220 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

CLNK
NM_052964.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -3.07

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:

ENSG00000287154 (HGNC:):

ENSG00000287154 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0021090806).

BP6

Variant 4-10525848-T-C is Benign according to our data. Variant chr4-10525848-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3043844.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CLNK	NM_052964.4 linkuse as main transcript	c.724A>G	p.Ile242Val	missense_variant	14/19	ENST00000226951.11	NP_443196.2
CLNK	XM_011513775.3 linkuse as main transcript	c.769A>G	p.Ile257Val	missense_variant	14/19		XP_011512077.1
CLNK	XM_017007684.2 linkuse as main transcript	c.769A>G	p.Ile257Val	missense_variant	14/19		XP_016863173.1
LOC105374482	XR_925387.4 linkuse as main transcript	n.262-4282T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLNK	ENST00000226951.11 linkuse as main transcript	c.724A>G	p.Ile242Val	missense_variant	14/19	1	NM_052964.4	ENSP00000226951.6		Q7Z7G1-1
ENSG00000287154	ENST00000663264.1 linkuse as main transcript	n.97-4286T>C		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00156

AC:

238

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00533

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000410

AC:

AN:

204976

Hom.:

AF XY:

0.000302

AC XY:

AN XY:

109346

show subpopulations

Gnomad AFR exome

AF:

0.00549

Gnomad AMR exome

AF:

0.000441

Gnomad ASJ exome

AF:

0.000109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000382

GnomAD4 exome

AF:

0.000154

AC:

220

AN:

1425900

Hom.:

Cov.:

AF XY:

0.000132

AC XY:

AN XY:

706534

show subpopulations

Gnomad4 AFR exome

AF:

0.00532

Gnomad4 AMR exome

AF:

0.000399

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000733

Gnomad4 OTH exome

AF:

0.000304

GnomAD4 genome

AF:

0.00156

AC:

238

AN:

152320

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

115

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00532

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000235

Hom.:

Bravo

AF:

0.00175

ESP6500AA

AF:

0.00487

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000374

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CLNK-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 28, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.0060

DANN

Benign

0.22

DEOGEN2

Benign

0.027

T;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0026

LIST_S2

Benign

0.40

T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;.

PrimateAI

Benign

0.26

PROVEAN

Benign

0.13

N;.

REVEL

Benign

0.064

Sift

Benign

0.23

T;.

Sift4G

Benign

0.64

T;T

Polyphen

0.0

B;.

Vest4

0.052

MVP

0.014

MPC

0.0068

ClinPred

0.019

GERP RS

-7.8

Varity_R

0.034

gMVP

0.16

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

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