Variant 4-10584947-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_052964.4(CLNK):c.92C>T(p.Pro31Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0523 in 1,613,330 control chromosomes in the GnomAD database, including 2,511 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P31S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.041 ( 187 hom., cov: 32)

Exomes 𝑓: 0.053 ( 2324 hom. )

Consequence

CLNK
NM_052964.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.92

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022577345).

BP6

Variant 4-10584947-G-A is Benign according to our data. Variant chr4-10584947-G-A is described in ClinVar as [Benign]. Clinvar id is 402545.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CLNK	NM_052964.4 linkuse as main transcript	c.92C>T	p.Pro31Leu	missense_variant	4/19	ENST00000226951.11
CLNK	XM_011513775.3 linkuse as main transcript	c.137C>T	p.Pro46Leu	missense_variant	4/19
CLNK	XM_017007684.2 linkuse as main transcript	c.137C>T	p.Pro46Leu	missense_variant	4/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLNK	ENST00000226951.11 linkuse as main transcript	c.92C>T	p.Pro31Leu	missense_variant	4/19	1	NM_052964.4	P1	Q7Z7G1-1
CLNK	ENST00000507719.1 linkuse as main transcript	c.-35C>T		5_prime_UTR_variant	4/13	1			Q7Z7G1-2

Frequencies

GnomAD3 genomes

AF:

0.0407

AC:

6190

AN:

152116

Hom.:

186

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0150

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.0384

Gnomad ASJ

AF:

0.0576

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0342

Gnomad FIN

AF:

0.0367

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0589

Gnomad OTH

AF:

0.0530

GnomAD3 exomes

AF:

0.0432

AC:

10731

AN:

248444

Hom.:

321

AF XY:

0.0454

AC XY:

6115

AN XY:

134728

show subpopulations

Gnomad AFR exome

AF:

0.0136

Gnomad AMR exome

AF:

0.0341

Gnomad ASJ exome

AF:

0.0566

Gnomad EAS exome

AF:

0.000279

Gnomad SAS exome

AF:

0.0393

Gnomad FIN exome

AF:

0.0400

Gnomad NFE exome

AF:

0.0570

Gnomad OTH exome

AF:

0.0499

GnomAD4 exome

AF:

0.0535

AC:

78149

AN:

1461096

Hom.:

2324

Cov.:

AF XY:

0.0538

AC XY:

39134

AN XY:

726774

show subpopulations

Gnomad4 AFR exome

AF:

0.0146

Gnomad4 AMR exome

AF:

0.0349

Gnomad4 ASJ exome

AF:

0.0577

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0394

Gnomad4 FIN exome

AF:

0.0386

Gnomad4 NFE exome

AF:

0.0593

Gnomad4 OTH exome

AF:

0.0477

GnomAD4 genome

AF:

0.0407

AC:

6190

AN:

152234

Hom.:

187

Cov.:

AF XY:

0.0405

AC XY:

3012

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0150

Gnomad4 AMR

AF:

0.0383

Gnomad4 ASJ

AF:

0.0576

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0342

Gnomad4 FIN

AF:

0.0367

Gnomad4 NFE

AF:

0.0589

Gnomad4 OTH

AF:

0.0525

Alfa

AF:

0.0552

Hom.:

401

Bravo

AF:

0.0402

TwinsUK

AF:

0.0596

AC:

221

ALSPAC

AF:

0.0651

AC:

251

ESP6500AA

AF:

0.0118

AC:

ESP6500EA

AF:

0.0617

AC:

515

ExAC

AF:

0.0426

AC:

5155

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.0638

EpiControl

AF:

0.0623

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

T;T

Eigen

Benign

0.14

Eigen_PC

Benign

0.084

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.58

T;T

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.3

L;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.6

D;.

REVEL

Benign

0.12

Sift

Uncertain

0.0010

D;.

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.99

D;.

Vest4

0.15

MPC

0.0065

ClinPred

0.027

GERP RS

3.9

Varity_R

0.13

gMVP

0.064

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