Variant 4-10490563-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_052964.4(CLNK):c.1191T>C(p.Ile397Ile) 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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.182

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 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 GnomAdExome4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CLNK	NM_052964.4 linkuse as main transcript	c.1191T>C	p.Ile397Ile	synonymous_variant	19/19	ENST00000226951.11	NP_443196.2
CLNK	XM_011513775.3 linkuse as main transcript	c.1236T>C	p.Ile412Ile	synonymous_variant	19/19		XP_011512077.1
LOC105374482	XR_925387.4 linkuse as main transcript	n.83+1368A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CLNK	ENST00000226951.11 linkuse as main transcript	c.1191T>C	p.Ile397Ile	synonymous_variant	19/19	1	NM_052964.4	ENSP00000226951.6	Q7Z7G1-1
CLNK	ENST00000515667.5 linkuse as main transcript	c.405T>C	p.Ile135Ile	synonymous_variant	5/5	3		ENSP00000427256.1	D6RJB9
ENSG00000287154	ENST00000663264.1 linkuse as main transcript	n.96+33723A>G		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00437

AC:

665

AN:

152172

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00440

AC XY:

517

AN XY:

117376

show subpopulations

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.:

Cov.:

AF XY:

0.00522

AC XY:

3739

AN XY:

716234

show subpopulations

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.:

Cov.:

AF XY:

0.00406

AC XY:

302

AN XY:

74460

show subpopulations

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.:

Bravo

AF:

0.00354

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

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

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