22-20917970-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_005207.4(CRKL):​c.36C>T​(p.Ser12Ser) 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 1,614,134 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

CRKL
NM_005207.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.81
Variant links:
Genes affected
CRKL (HGNC:2363): (CRK like proto-oncogene, adaptor protein) This gene encodes a protein kinase containing SH2 and SH3 (src homology) domains which has been shown to activate the RAS and JUN kinase signaling pathways and transform fibroblasts in a RAS-dependent fashion. It is a substrate of the BCR-ABL tyrosine kinase, plays a role in fibroblast transformation by BCR-ABL, and may be oncogenic.[provided by RefSeq, Jan 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
Variant 22-20917970-C-T is Benign according to our data. Variant chr22-20917970-C-T is described in ClinVar as [Benign]. Clinvar id is 785680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.82 with no splicing effect.
BS2
High AC in GnomAd4 at 472 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CRKLNM_005207.4 linkc.36C>T p.Ser12Ser synonymous_variant Exon 1 of 3 ENST00000354336.8 NP_005198.1 P46109
CRKLNR_156180.2 linkn.564C>T non_coding_transcript_exon_variant Exon 1 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CRKLENST00000354336.8 linkc.36C>T p.Ser12Ser synonymous_variant Exon 1 of 3 1 NM_005207.4 ENSP00000346300.3 P46109
CRKLENST00000411769.1 linkn.36C>T non_coding_transcript_exon_variant Exon 1 of 4 1 ENSP00000396646.1 P46109

Frequencies

GnomAD3 genomes
AF:
0.00311
AC:
473
AN:
152216
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0110
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.000788
AC:
197
AN:
250112
Hom.:
0
AF XY:
0.000613
AC XY:
83
AN XY:
135422
show subpopulations
Gnomad AFR exome
AF:
0.0108
Gnomad AMR exome
AF:
0.000521
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000532
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000315
AC:
460
AN:
1461800
Hom.:
0
Cov.:
31
AF XY:
0.000274
AC XY:
199
AN XY:
727200
show subpopulations
Gnomad4 AFR exome
AF:
0.0116
Gnomad4 AMR exome
AF:
0.000447
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:
0.0000108
Gnomad4 OTH exome
AF:
0.000563
GnomAD4 genome
AF:
0.00310
AC:
472
AN:
152334
Hom.:
3
Cov.:
32
AF XY:
0.00316
AC XY:
235
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.0110
Gnomad4 AMR
AF:
0.000588
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00163
Hom.:
0
Bravo
AF:
0.00360
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Sep 04, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

CRKL-related disorder Benign:1
Jun 27, 2019
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as 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
BayesDel_noAF
Benign
-0.45
CADD
Benign
5.7
DANN
Benign
0.95
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3

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.

Other links and lift over

dbSNP: rs150673692; hg19: chr22-21272258; API